Cancer Immunology, Immunotherapy

, Volume 58, Issue 11, pp 1723–1747 | Cite as

On the origin of serum CD26 and its altered concentration in cancer patients

  • Oscar J. CorderoEmail author
  • Francisco J. Salgado
  • Montserrat Nogueira


Dipeptidyl peptidase IV (DPP-IV), assigned to the CD26 cluster, is expressed on epithelial cells and lymphocytes and is a multifunctional or pleiotropic protein. Its peptidase activity causes degradation of many biologically active peptides, e.g. some incretins secreted by the enteroendocrine system. DPP-IV has, therefore, become a novel therapeutic target for inhibitors that extend endogenously produced insulin half-life in diabetics, and several reviews have appeared in recent months concerning the clinical significance of CD26/DPP-IV. Biological fluids contain relatively high levels of soluble CD26 (sCD26). The physiological role of sCD26 and its relation, if any, to CD26 functions, remain poorly understood because whether the process for CD26 secretion and/or shedding from cell membranes is regulated or not is not known. Liver epithelium and lymphocytes are often cited as the most likely source of sCD26. It is important to establish which tissue or organ is the protein source as well as the circumstances that can provoke an abnormal presence/absence or altered levels in many diseases including cancer, so that sCD26 can be validated as a clinical marker or a therapeutic target. For example, we have previously reported low levels of sCD26 in the blood of colorectal cancer patients, which indicated the potential usefulness of the protein as a biomarker for this cancer in early diagnosis, monitoring and prognosis. Through this review, we envisage a role for sCD26 and the alteration of normal peptidase capacity (in clipping enteroendocrine or other peptides) in the complex crosstalk between the lymphoid lineage and, at least, some malignant tumours.


sCD26 Dipeptidyl peptidase IV Cancer T cells Chemokines Incretins 



Dipeptidyl peptidase IV


Adenosine deaminase


Adenosine deaminase complexing protein



We thank M Páez de la Cadena and FJ Rodríguez-Berrocal for their suggestions and comments. This work was supported by grants (Ref.) PGIDT05PXIB20001PR and BFU2006-09717 from the Spanish administrations of the Xunta de Galicia (Secretaría Xeral de Investigación e Desenvolvemento) and the Ministerio de Educación y Ciencia (Dirección General de Investigación), respectively.


  1. 1.
    Dinjens WN et al (1989) Distribution of adenosine deaminase complexing protein (ADCP) in human tissues. J Histochem Cytochem 37(12):1869–1875PubMedGoogle Scholar
  2. 2.
    Lambeir AM et al (2003) Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40(3):209–294PubMedCrossRefGoogle Scholar
  3. 3.
    Hartel S et al (1988) Dipeptidyl peptidase (DPP) IV in rat organs. Comparison of immunohistochemistry and activity histochemistry. Histochemistry 89(2):151–161PubMedCrossRefGoogle Scholar
  4. 4.
    Fox DA et al (1984) Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody. J Immunol 133(3):1250–1256PubMedGoogle Scholar
  5. 5.
    Hegen M et al (1990) The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity. J Immunol 144(8):2908–2914PubMedGoogle Scholar
  6. 6.
    Yamabe T et al (1997) Induction of the 2B9 antigen/dipeptidyl peptidase IV/CD26 on human natural killer cells by IL-2, IL-12 or IL-15. Immunology 91(1):151–158PubMedCrossRefGoogle Scholar
  7. 7.
    Hopsu-Havu VK, Glenner GG (1966) A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-beta-naphthylamide. Histochemie 7(3):197–201PubMedCrossRefGoogle Scholar
  8. 8.
    Schrader WP, Stacy AR (1977) Purification and subunit structure of adenosine deaminase from human kidney. J Biol Chem 252(18):6409–6415PubMedGoogle Scholar
  9. 9.
    Morrison ME et al (1993) A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med 177(4):1135–1143PubMedCrossRefGoogle Scholar
  10. 10.
    Kameoka J et al (1993) Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science 261(5120):466–469PubMedCrossRefGoogle Scholar
  11. 11.
    Boonacker E, Van Noorden CJF (2003) The multifunctional or moonlighting protein CD26/DPPIV. Eur J Cell Biol 82(2):53–73PubMedCrossRefGoogle Scholar
  12. 12.
    De Meester I et al (1999) CD26, let it cut or cut it down. Immunol Today 20(8):367–375PubMedCrossRefGoogle Scholar
  13. 13.
    Ohnuma K, Dang NH, Morimoto C (2008) Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol 29(6):295–301PubMedCrossRefGoogle Scholar
  14. 14.
    Gorrell MD et al (2001) CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 54(3):249–264PubMedCrossRefGoogle Scholar
  15. 15.
    Busek P, Malík R, Sedo A (2004) Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer. Int J Biochem Cell Biol 36(3):408–421PubMedCrossRefGoogle Scholar
  16. 16.
    Sedo A et al (2008) Dipeptidyl peptidase-IV and related molecules: markers of malignancy? Expert Opin Med Diagn 2(6):1–13CrossRefGoogle Scholar
  17. 17.
    Salgado FJ et al (2003) A role for interleukin-12 in the regulation of T cell plasma membrane compartmentation. J Biol Chem 278(27):24849–24857PubMedCrossRefGoogle Scholar
  18. 18.
    Pacheco R et al (2005) CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse. Proc Natl Acad Sci USA 102(27):9583–9588PubMedCrossRefGoogle Scholar
  19. 19.
    Ren X et al (2005) Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels. Mol Cell Neurosci 29(2):320–332PubMedCrossRefGoogle Scholar
  20. 20.
    Ghersi G et al (2006) The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer Res 66(9):4652–4661PubMedCrossRefGoogle Scholar
  21. 21.
    Chen W-T, Kelly T (2003) Seprase complexes in cellular invasiveness. Cancer Metastasis Rev 22(2–3):259–269PubMedCrossRefGoogle Scholar
  22. 22.
    Cheng HC, Abdel-Ghany M, Pauli BU (2003) A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis. J Biol Chem 278(27):24600–24607PubMedCrossRefGoogle Scholar
  23. 23.
    Henry LR et al (2007) Clin Cancer Res 13(6):1736–1741PubMedCrossRefGoogle Scholar
  24. 24.
    Cheng JD et al (2005) Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth. Mol Cancer Ther 4(3):351–360PubMedGoogle Scholar
  25. 25.
    Morita A et al (1983) Intestinal assimilation of a proline-containing tetrapeptide. Role of a brush border membrane postproline dipeptidyl aminopeptidase IV. J Clin Invest 72(2):610–616PubMedCrossRefGoogle Scholar
  26. 26.
    Tiruppathi C et al (1993) Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides. Am J Physiol 265(1 Pt 1):G81–G89PubMedGoogle Scholar
  27. 27.
    Alfalah M, Jacob R, Naim HY (2002) Intestinal dipeptidyl peptidase IV is efficiently sorted to the apical membrane through the concerted action of N- and O-glycans as well as association with lipid microdomains. J Biol Chem 277(12):10683–10690PubMedCrossRefGoogle Scholar
  28. 28.
    Alfalah M et al (2005) A novel type of detergent-resistant membranes may contribute to an early protein sorting event in epithelial cells. J Biol Chem 280(52):42636–42643PubMedCrossRefGoogle Scholar
  29. 29.
    Vanhoof G et al (1995) Proline motifs in peptides and their biological processing. FASEB J 9(9):736–744PubMedGoogle Scholar
  30. 30.
    Murphy G, Murthy A, Khokha R (2008) Clipping, shedding and RIPping keep immunity on cue. Trends Immunol 29(2):75–82PubMedGoogle Scholar
  31. 31.
    Mentlein R, Gallwitz B, Schmidt WE (1993) Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 214:829–835PubMedCrossRefGoogle Scholar
  32. 32.
    Kieffer TJ, McIntosh CH, Pederson RA (1995) Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136(8):3585–3596PubMedCrossRefGoogle Scholar
  33. 33.
    Deacon CF, Johnsen AH, Holst JJ (1995) Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 80(3):952–957PubMedCrossRefGoogle Scholar
  34. 34.
    Hansen L et al (1999) Glucagon-like peptide-1-(7–36)amide is transformed to glucagon-like peptide-1-(9–36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology 140(11):5356–5363PubMedCrossRefGoogle Scholar
  35. 35.
    Nikolaidis LA et al (2005) Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289(6):H2401–H2408PubMedCrossRefGoogle Scholar
  36. 36.
    Jeppesen PB et al (2005) Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 54(9):1224–1231PubMedCrossRefGoogle Scholar
  37. 37.
    Deacon CF et al (2000) Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab 85(10):3575–3581PubMedCrossRefGoogle Scholar
  38. 38.
    Deacon CF et al (2001) Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic and antihyperglycemic effects in anesthetized pigs. Diabetes 50(7):1588–1597PubMedCrossRefGoogle Scholar
  39. 39.
    Pospisilik JA et al (2001) Metabolism of glucagon by dipeptidyl peptidase IV (CD26). Regul Pept 96(3):133–141PubMedCrossRefGoogle Scholar
  40. 40.
    Hinke SA et al (2000) Dipeptidyl peptidase IV (DPIV/CD26) degradation of glucagon. Characterization of glucagon degradation products and DPIV-resistant analogs. J Biol Chem 275(6):3827–3834PubMedCrossRefGoogle Scholar
  41. 41.
    Lambeir AM et al (2001) Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion. FEBS Lett 507(3):327–330PubMedCrossRefGoogle Scholar
  42. 42.
    Reeve JR Jr (1983) Amino acid sequences of three bombesin-like peptides from canine intestine extracts. J Biol Chem 258(9):5582–5588PubMedGoogle Scholar
  43. 43.
    Ballantyne GH (2006) Peptide YY(1–36) and peptide YY(3–36). Part II. Changes after gastrointestinal surgery and bariatric surgery. Obes Surg 16(6):795–803PubMedCrossRefGoogle Scholar
  44. 44.
    Ballantyne GH (2006) Peptide YY(1-36) and peptide YY(3-36). Part I. Distribution, release and actions. Obes Surg 16(5):651–658PubMedCrossRefGoogle Scholar
  45. 45.
    Jackson EK, Dubinion JH, Mi Z (2008) Effects of dipeptidyl peptidase IV inhibition on arterial blood pressure. Clin Exp Pharmacol Physiol 35(1):29–34PubMedCrossRefGoogle Scholar
  46. 46.
    Medeiros MD, Turner AJ (1994) Processing and metabolism of peptide-YY: pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11. Endocrinology 134(5):2088–2094PubMedCrossRefGoogle Scholar
  47. 47.
    Mentlein R (1999) Dipeptidyl-peptidase IV (CD26)—role in the inactivation of regulatory peptides. Regul Pept 85(1):9–24PubMedCrossRefGoogle Scholar
  48. 48.
    Byrd JB et al (2008) Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension 51(1):141–147PubMedCrossRefGoogle Scholar
  49. 49.
    Fryer RM et al (2008) Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema. Br J Pharmacol 153(5):947–955PubMedCrossRefGoogle Scholar
  50. 50.
    Pesquero JB et al (1992) Bradykinin metabolism pathway in the rat pulmonary circulation. J Hypertens 10(12):1471–1478PubMedCrossRefGoogle Scholar
  51. 51.
    Mentlein R, Roos T (1996) Proteases involved in the metabolism of angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), and neuropeptide Y by vascular smooth muscle cells. Peptides 17(4):709–720PubMedCrossRefGoogle Scholar
  52. 52.
    Brandt I et al (2006) Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin Chem 52(1):82–87PubMedCrossRefGoogle Scholar
  53. 53.
    Vanderheyden M (2008) Clinical importance of BNP truncation by DPPIV. Clin Chem Lab Med 46(4):A18Google Scholar
  54. 54.
    Abe K, Tilan JU, Zukowska Z (2007) NPY and NPY receptors in vascular remodeling. Curr Top Med Chem 7(17):1704–1709PubMedCrossRefGoogle Scholar
  55. 55.
    Kuo LE et al (2007) Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13(7):803–811PubMedCrossRefGoogle Scholar
  56. 56.
    Kitlinska J et al (2005) Differential effects of neuropeptide Y on the growth and vascularization of neural crest-derived tumors. Cancer Res 65(5):1719–1728PubMedCrossRefGoogle Scholar
  57. 57.
    Jarmołowska B et al (2007) Serum activity of dipeptidyl peptidase IV (DPPIV; EC in breast-fed infants with symptoms of allergy. Peptides 28(3):678–682PubMedCrossRefGoogle Scholar
  58. 58.
    Tiruppathi C et al (1990) Hydrolysis and transport of proline-containing peptides in renal brush-border membrane vesicles from dipeptidyl peptidase IV-positive and dipeptidyl peptidase IV-negative rat strains. J Biol Chem 256(3):1476–1483Google Scholar
  59. 59.
    Guieu R et al (2006) CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity. Behav Brain Res 166(2):230–235PubMedCrossRefGoogle Scholar
  60. 60.
    Bagosi Z et al (2006) The effects of endomorphins and diprotin A on striatal dopamine release induced by electrical stimulation—an in vitro superfusion study in rats. Neurochem Int 49(7):665–668PubMedCrossRefGoogle Scholar
  61. 61.
    Karl T et al (2003) Extreme reduction of dipeptidyl peptidase IV activity in F344 rat substrains is associated with various behavioral differences. Physiol Behav 80(1):123–134PubMedCrossRefGoogle Scholar
  62. 62.
    Grouzmann E et al (2002) Loss of dipeptidylpeptidase IV activity in chronic rhino sinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa. FASEB J 16(9):1132–1134PubMedGoogle Scholar
  63. 63.
    Busek P et al (2008) Modulation of substance P signaling by dipeptidyl peptidase-IV enzymatic activity in human glioma cell lines. Physiol Res 57(3):443–449PubMedGoogle Scholar
  64. 64.
    Proost P et al (2000) Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist. Blood 96(5):1674–1680PubMedGoogle Scholar
  65. 65.
    Struyf S et al (2001) Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils. Eur J Immunol 31(7):2170–2178PubMedCrossRefGoogle Scholar
  66. 66.
    Guan E, Wang J, Norcross MA (2004) Amino-terminal processing of MIP-1beta/CCL4 by CD26/dipeptidyl-peptidase IV. J Cell Biochem 92(1):53–64PubMedCrossRefGoogle Scholar
  67. 67.
    Campbell TB, Broxmeyer HE (2008) CD26 inhibition and hematopoiesis: a novel approach to enhance transplantation. Front Biosci 13:1795–1805PubMedCrossRefGoogle Scholar
  68. 68.
    Oravecz T et al (1997) Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage. J Exp Med 186(11):1865–1872PubMedCrossRefGoogle Scholar
  69. 69.
    Schols D et al (1998) CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity. Antiviral Res 39(3):175–187PubMedCrossRefGoogle Scholar
  70. 70.
    Proost P et al (1998) Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem 273(13):7222–7227PubMedCrossRefGoogle Scholar
  71. 71.
    Struyf S et al (1999) CD26/dipeptidyl-peptidase IV downregulates the eosinophil chemotactic potency, but not the anti-HIV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3. J Immunol 162(8):4903–4909PubMedGoogle Scholar
  72. 72.
    Forssmann U et al (2008) Inhibition of CD26/dipeptidyl peptidase IV enhances CCL11/eotaxin-mediated recruitment of eosinophils in vivo. J Immunol 181(2):1120–1127PubMedGoogle Scholar
  73. 73.
    Proost P et al (1999) Truncation of macrophage-derived chemokine by CD26/dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction. J Biol Chem 274(7):3988–3993PubMedCrossRefGoogle Scholar
  74. 74.
    Proost P et al (2001) Amino-terminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, while preserving antiangiogenic properties. Blood 98(13):3554–3561PubMedCrossRefGoogle Scholar
  75. 75.
    Proost P et al (2006) Natural posttranslational modifications of chemokines. Biochem Soc Trans 34(6):997–1001PubMedCrossRefGoogle Scholar
  76. 76.
    Proost P et al (2006) Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies. Arthritis Res Ther 8(4):R107PubMedCrossRefGoogle Scholar
  77. 77.
    Ludwig A et al (2002) Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine. J Leukoc Biol 72(1):183–191PubMedGoogle Scholar
  78. 78.
    Proost P et al (2007) Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration. Blood 110(1):37–44PubMedCrossRefGoogle Scholar
  79. 79.
    Ohtsuki T et al (1998) Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1alpha by CD26/dipeptidyl peptidase IV. FEBS Lett 431(2):236–240PubMedCrossRefGoogle Scholar
  80. 80.
    Proost P et al (1998) Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell derived factor-1alpha. FEBS Lett 432(1–2):73–76PubMedCrossRefGoogle Scholar
  81. 81.
    Shioda T et al (1998) Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha (SDF-1alpha) and SDF-1beta are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage. Proc Natl Acad Sci USA 95(11):6331–6336PubMedCrossRefGoogle Scholar
  82. 82.
    Struyf S et al (2003) Regulation of the immune response by the interaction of chemokines and proteases. Adv Immunol 81:1–44PubMedCrossRefGoogle Scholar
  83. 83.
    Sun YX et al (2008) CD26/dipeptidyl peptidase IV regulates prostate cancer metastasis by degrading SDF-1/CXCL12. Clin Exp Metastasis 25(7):765–776PubMedCrossRefGoogle Scholar
  84. 84.
    Nausch I et al (1990) The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta. Biol Chem Hoppe Seyler 371(11):1113–1118PubMedGoogle Scholar
  85. 85.
    Kahne T et al (1999) Dipeptidyl peptidase IV: a cell surface peptidase involved in regulating T cell growth. Int J Mol Med 4(1):3–15PubMedGoogle Scholar
  86. 86.
    Banbula A et al (2000) Emerging family of proline-specific peptidases of Porphyromonas gingivalis: purification and characterization of serine dipeptidyl peptidase, a structural and functional homologue of mammalian prolyl dipeptidyl peptidase IV. Infect Immun 68(3):1176–1182PubMedCrossRefGoogle Scholar
  87. 87.
    Reinhold D et al (2007) Dual inhibition of dipeptidyl peptidase IV and aminopeptidase N suppresses inflammatory immune responses. Ann N Y Acad Sci 1110:402–409PubMedCrossRefGoogle Scholar
  88. 88.
    Reinhold D et al (2008) DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis. Front Biosci 13:2356–2363PubMedCrossRefGoogle Scholar
  89. 89.
    Wolf M, Albrecht S, Märki C (2008) Proteolytic processing of chemokines: implications in physiological and pathological conditions. Int J Biochem Cell Biol 40(6–7):1185–1198PubMedCrossRefGoogle Scholar
  90. 90.
    Weihofen WA et al (2004) Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface. J Biol Chem 279(41):43330–43335PubMedCrossRefGoogle Scholar
  91. 91.
    Aertgeerts K et al (2004) N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding. Protein Sci 13(1):145–154PubMedCrossRefGoogle Scholar
  92. 92.
    Cuchacovich M et al (2001) Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases. Clin Exp Rheumatol 19(6):673–680PubMedGoogle Scholar
  93. 93.
    Christopherson KWII et al (2004) Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 305(5686):1000–1003PubMedCrossRefGoogle Scholar
  94. 94.
    Thielitz A et al (2008) The ectopeptidases dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related enzymes as possible targets in the treatment of skin diseases. Front Biosci 13:2364–2375PubMedCrossRefGoogle Scholar
  95. 95.
    Narra K et al (2007) Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer. Cancer Biol Ther 6(11):1691–1699PubMedCrossRefGoogle Scholar
  96. 96.
    Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132(6):2131–2157PubMedCrossRefGoogle Scholar
  97. 97.
    Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368(9548):1696–1705PubMedCrossRefGoogle Scholar
  98. 98.
    Baggio LL, Drucker DJ (2006) Therapeutic approaches to preserve islet mass in type 2 diabetes. Annu Rev Med 57:265–281PubMedCrossRefGoogle Scholar
  99. 99.
    Dinjens WN et al (1989) Distribution of adenosine deaminase-complexing protein in murine tissues. J Biol Chem 264(32):19215–19220PubMedGoogle Scholar
  100. 100.
    Deacon CF et al (1995) Both subcutaneously and intravenously administered glucagon-like peptide 1 are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 44(9):1126–1131PubMedCrossRefGoogle Scholar
  101. 101.
    Lankas GR et al (2005) Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 54(10):2988–2994PubMedCrossRefGoogle Scholar
  102. 102.
    Chyan YJ, Chuang LM (2007) Dipeptidyl peptidase IV inhibitors: an evolving treatment for type 2 diabetes from the incretin concept. Recent patents on endocrine. Metab Immune Drug Discov 1:15–24Google Scholar
  103. 103.
    Amori RE, Lau J, Pittas AG (2007) Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 298(2):194–206PubMedCrossRefGoogle Scholar
  104. 104.
    Grouzmann E et al (2007) Adverse effects of incretin therapy for type 2 diabetes. JAMA 298(15):1759–1760, author reply 1760PubMedCrossRefGoogle Scholar
  105. 105.
    Trotta PP, Balis ME (1978) Characterization of adenosine deaminase from normal coton and colon tumors. Evidence for tumor specific variants. Biochemistry 77(2):270–277CrossRefGoogle Scholar
  106. 106.
    Ten Kate J et al (1984) Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas. Cancer Res 44(10):4688–4692PubMedGoogle Scholar
  107. 107.
    Ten Kate J et al (1985) Immunohistochemical localization of adenosine deaminase complexing protein in intestinal mucosa and in colorectal adenocarcinoma as a marker for tumour cell heterogeneity. Histochem J 17(1):23–31PubMedCrossRefGoogle Scholar
  108. 108.
    Ten Kate J et al (1986) Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma. Int J Cancer 37(4):479–485PubMedCrossRefGoogle Scholar
  109. 109.
    Ten Kate J et al (1986) Adenosine deaminase complexing protein in cancer studies. Anticancer Res 6(5):983–988PubMedGoogle Scholar
  110. 110.
    Dinjens WN et al (1990) Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas. J Pathol 160(3):195–201PubMedCrossRefGoogle Scholar
  111. 111.
    Martín M et al (1995) Expression of ecto-adenosine deaminase and CD26 in human T cells triggered by the TCR-CD3 complex. Possible role of adenosine deaminase as costimulatory molecule. J Immunol 155(10):4630–4643PubMedGoogle Scholar
  112. 112.
    Cordero OJ et al (2001) Cytokines regulate membrane adenosine deaminase on human activated lymphocytes. J Leukoc Biol 70(6):920–930PubMedGoogle Scholar
  113. 113.
    Herrera C et al (2001) Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells. Mol Pharmacol 59(1):127–134PubMedGoogle Scholar
  114. 114.
    Hashikawa T et al (2004) Regulation of adenosine receptor engagement by ecto-adenosine deaminase. FASEB J 18(1):131–133PubMedGoogle Scholar
  115. 115.
    Ginés S et al (2002) Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction. Biochem J 361(2):203–209PubMedCrossRefGoogle Scholar
  116. 116.
    Iwata S, Morimoto C (1999) CD26/dipeptidyl peptidase IV in context. The different roles of a multifunctional ectoenzyme in malignant transformation. J Exp Med 190(3):301–306PubMedCrossRefGoogle Scholar
  117. 117.
    Lukashev D, Ohta A, Sitkovsky M (2007) Hypoxia-dependent anti-inflammatory pathways in protection of cancerous tissues. Cancer Metastasis Rev 26(2):273–279PubMedCrossRefGoogle Scholar
  118. 118.
    Hoskin DW et al (2008) Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells. Int J Oncol 32(3):527–535PubMedGoogle Scholar
  119. 119.
    White N, Burnstock G (2006) P2 receptors and cancer. Trends Pharmacol Sci 27(4):211–217PubMedCrossRefGoogle Scholar
  120. 120.
    Gonzalez-Gronow M et al (2008) Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor. Front Biosci 13:1610–1618PubMedCrossRefGoogle Scholar
  121. 121.
    Havre PA et al (2008) The role of CD26/dipeptidyl peptidase IV in cancer. Front Biosci 13:1634–1645PubMedCrossRefGoogle Scholar
  122. 122.
    Sedo A, Krepela E, Kasafírek E (1991) Dipeptidyl peptidase IV, prolyl endopeptidase and cathepsin B activities in primary human lung tumors and lung parenchyma. J Cancer Res Clin Oncol 117(3):249–253PubMedCrossRefGoogle Scholar
  123. 123.
    Asada Y et al (1993) Expression of dipeptidyl aminopeptidase IV activity in human lung carcinoma. Histopathology 23(3):265–270PubMedCrossRefGoogle Scholar
  124. 124.
    Krepela E et al (1996) Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma. Neoplasma 43(3):171–178PubMedGoogle Scholar
  125. 125.
    Park JE et al (1999) Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. J Biol Chem 274(51):36505–36512PubMedCrossRefGoogle Scholar
  126. 126.
    Davoodi J et al (2007) The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26. Proteomics 7(13):2300–2310PubMedCrossRefGoogle Scholar
  127. 127.
    Baumhoer D et al (2008) Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am J Clin Pathol 129(6):899–906PubMedCrossRefGoogle Scholar
  128. 128.
    Cheng W et al (2008) Glypican-3-mediated oncogenesis involves the insulin-like growth factor-signaling pathway. Carcinogenesis 29(7):1319–1326PubMedCrossRefGoogle Scholar
  129. 129.
    Jakubovic BD, Jothy S (2007) Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma. Exp Mol Pathol 82(2):184–189PubMedCrossRefGoogle Scholar
  130. 130.
    O’Brien P, O’Connor BF (2008) Seprase: an overview of an important matrix serine protease. Biochim Biophys Acta 1784(9):1130–1145PubMedGoogle Scholar
  131. 131.
    Ostermann E et al (2008) Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clin Cancer Res 14(14):4584–4592PubMedCrossRefGoogle Scholar
  132. 132.
    Huber MA et al (2003) Fibroblast activation protein: differential expression and serine protease activity in reactive stromal fibroblasts of melanocytic skin tumors. J Invest Dermatol 120(2):182–188PubMedCrossRefGoogle Scholar
  133. 133.
    Goscinski MA et al (2008) Seprase, dipeptidyl peptidase IV and Urokinase-type plasminogen activator expression in dysplasia and invasive squamous cell carcinoma of the esophagus. A study of 229 cases from Anyang Tumor Hospital, Henan Province, China. Oncology 75(1–2):49–59PubMedCrossRefGoogle Scholar
  134. 134.
    Werb Z (1997) ECM and cell surface proteolysis: regulating cellular ecology. Cell 91(4):439–442PubMedCrossRefGoogle Scholar
  135. 135.
    Piazza GA et al (1989) Evidence for a role of dipeptidyl peptidase IV in fibronectin-mediated interactions of hepatocytes with extracellular matrix. Biochem J 262(1):327–334PubMedGoogle Scholar
  136. 136.
    Scanlan MJ et al (1994) Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA 91(12):5657–5661PubMedCrossRefGoogle Scholar
  137. 137.
    Sneddon JB, Werb Z (2007) Location, location, location: the cancer stem cell niche. Cell Stem Cell 1(6):607–611PubMedCrossRefGoogle Scholar
  138. 138.
    Ruiz P et al (1998) CD26 expression and dipeptidyl peptidase IV activity in an aggressive hepatosplenic T-cell lymphoma. Cytometry 34(1):30–35PubMedCrossRefGoogle Scholar
  139. 139.
    Dang NH et al (2003) T-large granular lymphocyte lymphoproliferative disorder: expression of CD26 as a marker of clinically aggressive disease and characterization of marrow inhibition. Br J Haematol 121(5):857–865PubMedCrossRefGoogle Scholar
  140. 140.
    Carbone A et al (1995) The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkins-lymphomas leukemias. Blood 86(12):4617–4626PubMedGoogle Scholar
  141. 141.
    Bauvois B et al (1999) Constitutive expression of CD26/dipeptidylpeptidase IV on peripheral blood B lymphocytes of patients with B chronic lymphocytic leukaemia. Br J Cancer 79(7–8):1042–1048PubMedCrossRefGoogle Scholar
  142. 142.
    Hirai K et al (1999) Dipeptidyl peptidase IV (DPP IV/CD26) staining predicts distant metastasis of ‘benign’ thyroid tumor. Pathol Int 49(3):264–265PubMedCrossRefGoogle Scholar
  143. 143.
    de Micco C et al (2008) Utility of malignancy markers in fine-needle aspiration cytology of thyroid nodules: comparison of Hector Battifora mesothelial antigen-1, thyroid peroxidase and dipeptidyl aminopeptidase IV. Br J Cancer 98(4):818–823PubMedCrossRefGoogle Scholar
  144. 144.
    Stremenova J et al (2007) Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade. Int J Oncol 31(4):785–792PubMedGoogle Scholar
  145. 145.
    Yamaguchi U et al (2008) Distinct gene expression-defined classes of gastrointestinal stromal tumor. J Clin Oncol 26(25):4100–4108PubMedCrossRefGoogle Scholar
  146. 146.
    Cro L et al (2009) CD26 expression in mature B-cell neoplasia: its possible role as a new prognostic marker in B-CLL. Hematol Oncol Feb 26 on-lineGoogle Scholar
  147. 147.
    Carlucci F et al (2009) A 57-gene expression signature in B-cell chronic lymphocytic leukemia. Biomed Pharmacother. doi: 10.1016/j.biopha.2009.02.001
  148. 148.
    Wilson MJ et al (2005) Elevation of dipeptidylpeptidase IV activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker. J Urol 74(3):1124–1128CrossRefGoogle Scholar
  149. 149.
    Sedo A, Krepela E, Kasafirek E (1991) Dipeptidyl peptidase IV, prolyl endopeptidase and cathepsin B activities in primary human lung tumors and lung parenchyma. J Cancer Res Clin Oncol 117(3):249–253PubMedCrossRefGoogle Scholar
  150. 150.
    Kojima J et al (1987) Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl-transferase transpeptidase in human hepatic cancer and embryonal tissues. Clin Chim Acta 167(3):285–291PubMedCrossRefGoogle Scholar
  151. 151.
    Moehrle MC et al (1995) Aminopeptidase-M and dipeptidyl peptidase-IV activity in epithelial skin tumors—a histochemical-study. J Cutan Pathol 22(3):241–247PubMedCrossRefGoogle Scholar
  152. 152.
    Roesch A et al (2006) Loss of dipeptidyl peptidase IV immunostaining discriminates malignant melanomas from deep penetrating nevi. Mod Pathol 19(10):1378–1385PubMedCrossRefGoogle Scholar
  153. 153.
    Inamoto T et al (2007) Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. Clin Cancer Res 13(14):4191–4200PubMedCrossRefGoogle Scholar
  154. 154.
    Inamoto T et al (2006) Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cyclin-dependent kinase 2 reduction, p27(kip1) enhancement, and disruption of binding to the extracellular matrix. Clin Cancer Res 12(11 Pt1):3470–3477PubMedCrossRefGoogle Scholar
  155. 155.
    Verstovsek S, Cabanillas F, Dang NH (2000) CD26 in T-cell lymphomas: a potential clinical role? Oncology (Huntingt) 14(6 Suppl 2):17–23Google Scholar
  156. 156.
    Jones D et al (2001) Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood. Am J Clin Pathol 115(6):885–892PubMedCrossRefGoogle Scholar
  157. 157.
    Bernengo MG et al (2001) The relevance of the CD4+ CD26− subset in the identification of circulating Sézary cells. Br J Dermatol 144(1):125–135PubMedCrossRefGoogle Scholar
  158. 158.
    Kondo S et al (1996) Expression of CD26/dipeptidyl peptidase IV in adult T cell leukemia/lymphoma (ATLL). Leuk Res 20(4):357–363PubMedCrossRefGoogle Scholar
  159. 159.
    Van den Oord JJ (1998) Expression of CD26/dipeptidyl-peptidase IV in benign and malignant pigment-cell lesions of the skin. Br J Dermatol 138(4):615–621PubMedCrossRefGoogle Scholar
  160. 160.
    Khin EE et al (2003) Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am J Obstet Gynecol 188(3):670–676PubMedCrossRefGoogle Scholar
  161. 161.
    Kajiyama H et al (2003) Expression of CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma and its negative correlation with tumor grade. Adv Exp Med Biol 524:245–248PubMedCrossRefGoogle Scholar
  162. 162.
    Bogenrieder T et al (1997) Expression and localization of aminopeptidase A, aminopeptidase N, and dipeptidyl peptidase IV in benign and malignant human prostate tissue. Prostate 33(4):225–232PubMedCrossRefGoogle Scholar
  163. 163.
    Houghton AN et al (1988) Cell surface antigens of human melanocytes and melanoma. Expression of adenosine deaminase binding protein is extinguished with melanocyte transformation. J Exp Med 167(1):197–212PubMedCrossRefGoogle Scholar
  164. 164.
    Morrison ME et al (1993) A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase. J Exp Med 177(4):1135–1143PubMedCrossRefGoogle Scholar
  165. 165.
    Albino AP et al (1992) Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype. Oncogene 7(11):2315–2321PubMedGoogle Scholar
  166. 166.
    Wesley UV et al (1999) A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med 190(3):311–322PubMedCrossRefGoogle Scholar
  167. 167.
    Wesley UV et al (2004) Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells. Int J Cancer 109(6):855–866PubMedCrossRefGoogle Scholar
  168. 168.
    Wesley UV, McGroarty M, Homoyouni A (2005) Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res 65(4):1325–1334PubMedCrossRefGoogle Scholar
  169. 169.
    Kajiyama H et al (2002) Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res 62(10):2753–2757PubMedGoogle Scholar
  170. 170.
    Kikkawa F et al (2005) Dipeptidyl peptidase IV in tumor progression. Biochim Biophys Acta 1751(1):45–51PubMedGoogle Scholar
  171. 171.
    Busek P, Stremenova J, Sedo A (2008) Dipeptidyl peptidase-IV enzymatic activity bearing molecules in human brain tumors-good or evil? Front Biosci 13:2319–2326PubMedCrossRefGoogle Scholar
  172. 172.
    Preller V et al (2007) TGF-beta1-mediated control of central nervous system inflammation and autoimmunity through the inhibitory receptor CD26. J Immunol 178(7):4632–4640PubMedGoogle Scholar
  173. 173.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867PubMedCrossRefGoogle Scholar
  174. 174.
    Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296PubMedCrossRefGoogle Scholar
  175. 175.
    Steinbrecher A et al (2001) Targeting dipeptidyl peptidase IV (CD26) suppresses autoimmune encephalomyelitis and up-regulates TGF-beta 1 secretion in vivo. J Immunol 166(3):2041–2048PubMedGoogle Scholar
  176. 176.
    Shingu K et al (2003) CD26 expression determines lung metastasis in mutant F344 rats: involvement of NK cell function and soluble CD26. Cancer Immunol Immunother 52(9):546–554PubMedCrossRefGoogle Scholar
  177. 177.
    Nagatsu I, Nagatsu T, Yamamoto T (1968) Hydrolysis of amino acid beta-naphthylamides by aminopeptidases in human parotid salva and human serum. Experientia 24(4):347–348PubMedCrossRefGoogle Scholar
  178. 178.
    Smith RE et al (1998) The significance of hypersialylation of dipeptidyl peptidase IV (CD26) in the inhibition of its activity by Tat and other cationic peptides. CD26: a subvertid adhesion molecule for HIV peptide binding. AIDS Res Hum Retroviruses 14(10):851–868PubMedCrossRefGoogle Scholar
  179. 179.
    Blanc G et al (2007) Insights into how CUB domains can exert specific functions while sharing a common fold: conserved and specific features of the CUB1 domain contribute to the molecular basis of procollagen C-proteinase enhancer-1 activity. J Biol Chem 282(23):16924–16933PubMedCrossRefGoogle Scholar
  180. 180.
    Wermter C et al (2007) The protease domain of procollagen C-proteinase (BMP1) lacks substrate selectivity, which is conferred by non-proteolytic domains. Biol Chem 388(5):513–521PubMedCrossRefGoogle Scholar
  181. 181.
    Gunn TM et al (1999) The mouse mahogany locus encodes a transmembrane form of human attractin. Nature 398(6723):152–156PubMedCrossRefGoogle Scholar
  182. 182.
    Duke-Cohan JS et al (1995) A novel form of dipeptidylpeptidase IV found in human serum. Isolation, characterization, and comparison with T lymphocyte membrane dipeptidylpeptidase IV (CD26). J Biol Chem 270(23):14107–14114PubMedCrossRefGoogle Scholar
  183. 183.
    Duke-Cohan JS et al (1996) Serum high molecular weight dipeptidyl peptidase IV (CD26) is similar to a novel antigen DPPT-L released from activated T cells. J Immunol 156(5):1714–1721PubMedGoogle Scholar
  184. 184.
    Friedrich D et al (2007) Does human attractin have DP4 activity? Biol Chem 388(2):155–162PubMedCrossRefGoogle Scholar
  185. 185.
    Tang W et al (2000) Secreted and membrane attractin result from alternative splicing of the human ATRN gene. Proc Natl Acad Sci USA 97(11):6025–6030PubMedCrossRefGoogle Scholar
  186. 186.
    Schrader WP, Woodward FJ, Pollara B (1979) Purification of an adenosine deaminase complexing protein from human plasma. J Biol Chem 254(23):11964–11968PubMedGoogle Scholar
  187. 187.
    Iwaki-Egawa S et al (1998) Dipeptidyl peptidase IV from human serum: purification, characterization, and N-terminal amino acid sequence. J Biochem (Tokyo) 124(2):428–433Google Scholar
  188. 188.
    Durinx C et al (2000) Molecular characterization of dipeptidyl peptidase activity in serum. Soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides. Eur J Biochem 267(17):5608–5613PubMedCrossRefGoogle Scholar
  189. 189.
    Watanabe Y et al (1998) Aminopeptidase N in sera of healthy subjects is a different N-terminal processed derivative from the one obtained from maternal serum. Mol Genet Metab 63(4):289–294PubMedCrossRefGoogle Scholar
  190. 190.
    Watanabe Y et al (1995) Identification of an alanine aminopeptidase in human maternal serum as a membrane-bound aminopeptidase N. Biol Chem Hoppe Seyler 376(7):397–400PubMedGoogle Scholar
  191. 191.
    Hooper NM, Karran EH, Turner AJ (1997) Membrane protein secretases. Biochem J 321(2):265–279PubMedGoogle Scholar
  192. 192.
    Bauvois B et al (2000) Regulation of CD26/DPPIV gene expression by interferons and retinoic acid in tumor B cells. Oncogene 19(2):265–272PubMedCrossRefGoogle Scholar
  193. 193.
    Schade J et al (2008) Regulation of expression and function of dipeptidyl peptidase 4 (DP4), DP8/9, and DP10 in allergic responses of the lung in rats. J Histochem Cytochem 56(2):147–155PubMedCrossRefGoogle Scholar
  194. 194.
    Danielsen EM, Cowell GM, Poulsen SS (1983) Biosynthesis of intestinal microvillar proteins. Role of the Golgi complex and microtubules. Biochem J 216(1):37–42PubMedGoogle Scholar
  195. 195.
    Arribas J et al (1996) Diverse cell surface protein ectodomains are shed by a system sensitive to metalloprotease inhibitors. J Biol Chem 271(19):11376–11382PubMedCrossRefGoogle Scholar
  196. 196.
    Lemberg MK, Freeman M (2007) Cutting proteins within lipid bilayers: rhomboid structure and mechanism. Mol Cell 28(6):930–940PubMedCrossRefGoogle Scholar
  197. 197.
    Grondin G, Hooper NM, LeBel D (1999) Specific localization of membrane dipeptidase and dipeptidyl peptidase IV in secretion granules of two different pancreatic islet cells. J Histochem Cytochem 47(4):489–498PubMedGoogle Scholar
  198. 198.
    Poulsen MD et al (1993) Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells. J Histochem Cytochem 41(1):81–88PubMedGoogle Scholar
  199. 199.
    Macnair DC, Kenny AJ (1979) Proteins of the kidney microvillar membrane. The amphipathic form of dipeptidyl peptidase IV. Biochem J 179(2):379–395PubMedGoogle Scholar
  200. 200.
    Böhm SK et al (1995) Human dipeptidyl peptidase IV gene promoter: tissue-specific regulation from a TATA-less GC-rich sequence characteristic of a housekeeping gene promoter. Biochem J 311(3):835–843PubMedGoogle Scholar
  201. 201.
    Teague TK et al (1999) Activation changes the spectrum but not the diversity of genes expressed by T cells. Proc Natl Acad Sci USA 96(22):12691–12696PubMedCrossRefGoogle Scholar
  202. 202.
    Rogge L et al (2000) Transcript imaging of the development of human T helper cells using oligonucleotide arrays. Nat Genet 25(1):96–101PubMedCrossRefGoogle Scholar
  203. 203.
    Mattern T et al (1995) Antibody-induced modulation of CD26 surface expression. Immunology 84(4):60–595Google Scholar
  204. 204.
    Salgado FJ et al (2000) Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes. Cytokine 12(7):1136–1141PubMedCrossRefGoogle Scholar
  205. 205.
    Beau I, Berger A, Servin AL (2007) Rotavirus impairs the biosynthesis of brush-border-associated dipeptidyl peptidase IV in human enterocyte-like Caco-2/TC7 cells. Cell Microbiol 9(3):779–789PubMedCrossRefGoogle Scholar
  206. 206.
    Hama T et al (1982) Purification of dipeptidyl-aminopeptidase IV from human kidney by anti dipeptidyl-aminopeptidase IV affinity chromatography. Mol Cell Biochem 43(1):35–42PubMedGoogle Scholar
  207. 207.
    Krepela E et al (1983) Demonstration of two molecular forms of dipeptidyl peptidase IV in normal human serum. Physiol Bohemoslov 32(6):486–496PubMedGoogle Scholar
  208. 208.
    Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579PubMedGoogle Scholar
  209. 209.
    Mignot G et al (2006) Prospects for exosomes in immunotherapy of cancer. J Cell Mol Med 10(2):376–388PubMedCrossRefGoogle Scholar
  210. 210.
    Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9(6):871–881PubMedCrossRefGoogle Scholar
  211. 211.
    Gatti JL et al (2005) Identification, proteomic profiling, and origin of ram epididymal fluid exosome-like vesicles. Biol Reprod 72(6):1452–1465PubMedCrossRefGoogle Scholar
  212. 212.
    Mallegol J, van Niel G, Heyman M (2005) Phenotypic and functional characterization of intestinal epithelial exosomes. Blood Cells Mol Dis 35(1):11–16PubMedCrossRefGoogle Scholar
  213. 213.
    Ogawa Y et al (2008) Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol Pharm Bull 31(6):1059–1062PubMedCrossRefGoogle Scholar
  214. 214.
    Busso N et al (2005) Circulating CD26 is negatively associated with inflammation in human and experimental arthritis. Am J Pathol 166(2):433–442PubMedGoogle Scholar
  215. 215.
    Narducci MG et al (2006) Skin homing of Sezary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV. Blood 107(3):1108–1115PubMedCrossRefGoogle Scholar
  216. 216.
    Iwaki-Egawa S, Watanabe Y, Fujimoto Y (1995) Is CD26/dipeptidyl peptidase IV a really important molecule in T cell activation of a certain rat strain? Immunobiology 194(4–5):429–442PubMedGoogle Scholar
  217. 217.
    Marguet D et al (2000) Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 97(12):6874–6879PubMedCrossRefGoogle Scholar
  218. 218.
    Yan S et al (2003) Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen. Eur J Immunol 33(6):1519–1527PubMedCrossRefGoogle Scholar
  219. 219.
    Nagatsu T, Sakai T, Kojima K (1985) A sensitive and specific assay for dipeptidyl-aminopeptidase II in serum and tissues by liquid chromatography-fluorometry. Anal Biochem 147(1):80–85PubMedCrossRefGoogle Scholar
  220. 220.
    Kojima K, Mihara R, Sakai T (1987) Serum activities of dipeptidyl-aminopeptidase II and dipeptidyl-aminopeptidase IV in tumor-bearing animals and in cancer patients. Biochem Med Metab Biol 37(1):35–41PubMedCrossRefGoogle Scholar
  221. 221.
    Maes MB, Scharpé S, De Meester I (2007) Dipeptidyl peptidase II (DPPII), a review. Clin Chim Acta 380(1–2):31–49PubMedCrossRefGoogle Scholar
  222. 222.
    Rosenblum JS, Kozarich JW (2003) Prolyl peptidases: a serine protease subfamily with high potential for drug discovery. Curr Opin Chem Biol 7(4):496–504PubMedCrossRefGoogle Scholar
  223. 223.
    Maes MB et al (2005) Kinetic investigation of human dipeptidyl peptidase II (DPPII)-mediated hydrolysis of dipeptide derivatives and its identification as quiescent cell proline dipeptidase (QPP)/dipeptidyl peptidase 7 (DPP7). Biochem J 386(2):315–324PubMedCrossRefGoogle Scholar
  224. 224.
    Araki H et al (2001) Purification, molecular cloning, and immunohistochemical localization of dipeptidyl peptidase II from the rat kidney and its identity with quiescent cell proline dipeptidase. J Biochem 129(2):279–288PubMedGoogle Scholar
  225. 225.
    Underwood R et al (1999) Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase. J Biol Chem 274(48):34053–34058PubMedCrossRefGoogle Scholar
  226. 226.
    Chiravuri M et al (2000) Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase. J Immunol 165(10):5695–5702PubMedGoogle Scholar
  227. 227.
    Chiravuri M et al (2000) Homodimerization via a leucine zipper motif is required for enzymatic activity of quiescent cell proline dipeptidase. J Biol Chem 275(35):26994–26999PubMedGoogle Scholar
  228. 228.
    Chiravuri M, Huber BT (2000) Aminodipeptidase inhibitor-induced cell death in quiescent lymphocytes: a review. Apoptosis 5(4):319–322PubMedCrossRefGoogle Scholar
  229. 229.
    Maes MB et al (2006) Dipeptidyl peptidase II and leukocyte cell death. Biochem Pharmacol 72(1):70–79PubMedCrossRefGoogle Scholar
  230. 230.
    Struckhoff G, Heymann E (1986) Rat peritoneal mast cells release dipeptidyl peptidase II. Biochem J 236(1):215–219PubMedGoogle Scholar
  231. 231.
    Klener P et al (1987) Possible prognostic significance of the assessment of dipeptidylpeptidase II in peripheral blood lymphocytes of patients with chronic lymphocytic leukemia. Neoplasma 34(5):581–586PubMedGoogle Scholar
  232. 232.
    Danilov AV et al (2005) Differential control of G0 programme in chronic lymphocytic leukaemia: a novel prognostic factor. Br J Haematol 128(4):472–481PubMedCrossRefGoogle Scholar
  233. 233.
    Urade M et al (1989) Serum dipeptidyl peptidase activities as a possible marker of oral cancer. Cancer 64(6):1274–1280PubMedCrossRefGoogle Scholar
  234. 234.
    Mogi M et al (1986) Sandwich enzyme-immunoassay for dipeptidyl aminopeptidase IV in the serum of people with oral cancer. Arch Oral Biol 31(7):505–507PubMedCrossRefGoogle Scholar
  235. 235.
    Lee KN et al (2004) A novel plasma proteinase potentiates alpha2-antiplasmin inhibition of fibrin digestion. Blood 103(10):3783–3788PubMedCrossRefGoogle Scholar
  236. 236.
    Lee KN et al (2006) Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein. Blood 107(4):1397–1404PubMedCrossRefGoogle Scholar
  237. 237.
    Christiansen VJ et al (2007) The effect of a single nucleotide polymorphism on human alpha 2-antiplasmin activity. Blood 109(12):5286–5292PubMedCrossRefGoogle Scholar
  238. 238.
    Collins PJ et al (2004) Purification, identification and characterisation of seprase from bovine serum. Int J Biochem Cell Biol 36(11):2320–2333PubMedCrossRefGoogle Scholar
  239. 239.
    Aimes RT et al (2003) Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost 89(3):561–572PubMedGoogle Scholar
  240. 240.
    Chen D et al (2006) Activation of EDTA-resistant gelatinases in malignant human tumors. Cancer Res 66(20):9977–9985PubMedCrossRefGoogle Scholar
  241. 241.
    Cordero OJ et al (2000) Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer. Br J Cancer 83(9):1139–1146PubMedCrossRefGoogle Scholar
  242. 242.
    Ayude D et al (2004) Clinical interest of the combined use of serum CD26 and alpha-l-fucosidase in the early detection diagnosis of colorectal cancer. Dis Markers 19(6):267–272Google Scholar
  243. 243.
    Cordero OJ et al (2008) Validation of serum CD26 as a screening marker for colorectal cancer. Clin Chem Lab Med 46(4):A23Google Scholar
  244. 244.
    Cordero OJ et al (2008) How the measurements of a few serum markers can be combined to enhance their clinical values in the management of cancer. Anticancer Res 28(4):2333–2341PubMedGoogle Scholar
  245. 245.
    de la Haba-Rodríguez J et al (2002) Soluble dipeptidyl peptidase IV (CD-26) in serum of patients with colorectal carcinoma. Neoplasma 49(5):307–311PubMedGoogle Scholar
  246. 246.
    Cordero OJ et al (2001) Interleukin 12, interleukin 15, soluble CD26 and adenosine deaminase levels in the sera of rheumatoid arthritis patients. Rheumatol Int 21(2):69–74PubMedCrossRefGoogle Scholar
  247. 247.
    Ellingsen T et al (2007) In active chronic rheumatoid arthritis, dipeptidyl peptidase IV density is increased on monocytes and CD4(+) T lymphocytes. Scand J Immunol 66(4):451–457PubMedCrossRefGoogle Scholar
  248. 248.
    Cuchacovich M et al (2002) Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients. Clin Diagn Lab Immunol 9(6):1253–1259PubMedGoogle Scholar
  249. 249.
    Kobayashi H et al (2002) Reduction of serum soluble CD26/dipeptidyl peptidase IV enzyme activity and its correlation with disease activity in systemic lupus erythematosus. J Rheumatol 29(9):1858–1866PubMedGoogle Scholar
  250. 250.
    Tamaki Z et al (2008) Serum levels of soluble CD26 in patients with scleroderma. J Dermatol Sci 52(1):67–69PubMedCrossRefGoogle Scholar
  251. 251.
    Lun SW et al (2007) Increased expression of plasma and CD4+ T lymphocyte costimulatory molecule CD26 in adult patients with allergic asthma. J Clin Immunol 27(4):430–437PubMedCrossRefGoogle Scholar
  252. 252.
    Katoh N et al (2000) Soluble CD30 is more relevant to disease activity of atopic dermatitis than soluble CD26. Clin Exp Immunol 121(2):187–192PubMedCrossRefGoogle Scholar
  253. 253.
    Schönermarck U et al (2000) Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clin Exp Rheumatol 18(4):457–463PubMedGoogle Scholar
  254. 254.
    Hosono O et al (1999) Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals. Clin Immunol 91(3):283–295PubMedCrossRefGoogle Scholar
  255. 255.
    Yang SS et al (2006) Changes of soluble CD26 and CD30 levels correlate with response to interferon plus ribavirin therapy in patients with chronic hepatitis C. J Gastroenterol Hepatol 21(12):1789–1793PubMedCrossRefGoogle Scholar
  256. 256.
    Itou M et al (2008) Altered expression of glucagon-like peptide-1 and dipeptidyl peptidase IV in patients with HCV-related glucose intolerance. J Gastroenterol Hepatol 23(2):244–251PubMedCrossRefGoogle Scholar
  257. 257.
    Ajdary S et al (2006) Soluble CD26/CD30 levels in visceral leishmaniasis: markers of disease activity. Clin Exp Immunol 145(1):44–47PubMedCrossRefGoogle Scholar
  258. 258.
    Ajdary S et al (2007) Soluble CD26 and CD30 levels in patients with anthroponotic cutaneous leishmaniasis. J Infect 55(1):75–78PubMedCrossRefGoogle Scholar
  259. 259.
    Durinx C et al (2001) Reference values for plasma dipeptidylpeptidase IV activity and their association with other laboratory parameters. Clin Chem Lab Med 39(2):155–159PubMedCrossRefGoogle Scholar
  260. 260.
    Scharpé S et al (1988) Assay of dipeptidyl peptidase IV in serum by fluorometry of 4-methoxy-2-naphthylamine. Clin Chem 34(11):2299–2301PubMedGoogle Scholar
  261. 261.
    Hino M et al (1975) Glycylprolyl beta-naphthylamidase activity in human serum. Clin Chim Acta 62(1):5–11PubMedCrossRefGoogle Scholar
  262. 262.
    Fuyamada H et al (1977) Serum glycylproline p-nitroanilidase activity in human hypertension. Clin Chim Acta 74(2):177–181PubMedCrossRefGoogle Scholar
  263. 263.
    Fujita K et al (1977) Serum glycylproline p-nitroanilidase activity in blood cancers. Clin Chim Acta 81(2):215–217PubMedCrossRefGoogle Scholar
  264. 264.
    Kojima J et al (1979) Serum glycylproline dipeptidyl aminopeptidase activity in human hepatic cancer. Clin Chim Acta 93(2):181–187PubMedCrossRefGoogle Scholar
  265. 265.
    Yoshii Y et al (1981) Changes in serum dipeptidyl-aminopeptidase IV (glycylprolyl dipeptidyl-aminopeptidase) activity of patients with gastric carcinoma after surgical excision and the enzyme activity in the carcinoma tissue. Biochem Med 25(3):276–282PubMedCrossRefGoogle Scholar
  266. 266.
    Kojima K et al (1987) Serum activities of dipeptidyl-aminopeptidase II and dipeptidyl-aminopeptidase IV in tumor-bearing animals and in cancer patients. Biochem Med Metab Biol 37(1):35–41PubMedCrossRefGoogle Scholar
  267. 267.
    Fukasawa K et al (1982) Serum dipeptidyl peptidase (DPP) IV activities in oral cancer patients. Int J Oral Surg 11(4):246–250PubMedCrossRefGoogle Scholar
  268. 268.
    Urade M et al (1989) Serum dipeptidyl peptidase activities as a possible marker of oral cancer. Cancer 64(6):1274–1280PubMedCrossRefGoogle Scholar
  269. 269.
    Hagihara M, Ohhashi M, Nagatsu T (1987) Activities of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice with lupus erythematosus-like syndrome and in patients with lupus erythematosus and rheumatoid arthritis. Clin Chem 33(8):1463–1465PubMedGoogle Scholar
  270. 270.
    Gotoh H et al (1988) Activity of dipeptidyl peptidase IV and post-proline cleaving enzyme in sera from osteoporotic patients. Clin Chem 34(12):2499–2501PubMedGoogle Scholar
  271. 271.
    Stancíková M et al (1992) Dipeptidyl peptidase IV in patients with systemic lupus erythematosus. Clin Exp Rheumatol 10(4):381–385PubMedGoogle Scholar
  272. 272.
    Bergmann A, Bohuon C (2002) Decrease of serum dipeptidylpeptidase activity in severe sepsis patients: relationship to procalcitonin. Clin Chim Acta 321(1–2):123–126PubMedCrossRefGoogle Scholar
  273. 273.
    Perner F et al (1999) Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence. J Lab Clin Med 134(1):56–67PubMedCrossRefGoogle Scholar
  274. 274.
    Andrieu T et al (2003) Similar increased serum dipeptidyl peptidase IV activity in chronic hepatitis C and other viral infections. J Clin Virol 27(1):59–68PubMedCrossRefGoogle Scholar
  275. 275.
    Lakatos PL et al (1999) Elevated serum dipeptidyl peptidase IV (CD26, EC activity in patients with primary biliary cirrhosis. J Hepatol 30(4):740PubMedCrossRefGoogle Scholar
  276. 276.
    Balaban YH et al (2007) Dipeptidyl peptidase IV (DDP IV) in NASH patients. Ann Hepatol 6(4):242–250PubMedGoogle Scholar
  277. 277.
    Meneilly GS et al (2000) Effect of ageing and diabetes on glucose-dependent insulinotropic polypeptide and dipeptidyl peptidase IV responses to oral glucose. Diabet Med 17(5):346–350PubMedCrossRefGoogle Scholar
  278. 278.
    Mannucci E et al (2005) Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus. Diabetologia 48(6):1168–1172PubMedCrossRefGoogle Scholar
  279. 279.
    Hildebrandt M et al (2001) Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease. Scand J Gastroenterol 36(10):1067–1072PubMedCrossRefGoogle Scholar
  280. 280.
    Xiao Q et al (2000) Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease. Am J Physiol Regul Integr Comp Physiol 278(4):R1057–R1063PubMedGoogle Scholar
  281. 281.
    Rose M et al (2002) T-cell immune parameters and depression in patients with Crohn’s disease. J Clin Gastroenterol 34(1):40–48PubMedCrossRefGoogle Scholar
  282. 282.
    van der Velden VH et al (1999) Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics—comparison with healthy non-smokers and smokers and effects of inhaled glucocorticoids. Clin Exp Allergy 29(6):813–823CrossRefGoogle Scholar
  283. 283.
    Jarmołowska B et al (2007) Serum activity of dipeptidyl peptidase IV (DPPIV; EC in breast-fed infants with symptoms of allergy. Peptides 28(3):678–682PubMedCrossRefGoogle Scholar
  284. 284.
    Detel D, Persić M, Varljen J (2007) Serum and intestinal dipeptidyl peptidase IV (DPP IV/CD26) activity in children with celiac disease. J Pediatr Gastroenterol Nutr 45(1):65–70PubMedCrossRefGoogle Scholar
  285. 285.
    Maes M et al (1999) Lower activity of serum peptidases in abstinent alcohol-dependent patients. Alcohol 17(1):1–6PubMedCrossRefGoogle Scholar
  286. 286.
    Maes M et al (1998) Effects of psychological stress on serum prolyl endopeptidase and dipeptidyl peptidase IV activity in humans: higher serum prolyl endopeptidase activity is related to stress-induced anxiety. Psychoneuroendocrinology 23(5):485–495PubMedCrossRefGoogle Scholar
  287. 287.
    Maes M et al (1997) Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers. Psychoneuroendocrinology 22(2):65–78PubMedCrossRefGoogle Scholar
  288. 288.
    Maes M et al (1996) Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs. Acta Psychiatr Scand 93(1):1–8PubMedCrossRefGoogle Scholar
  289. 289.
    Elgün S, Keskinege A, Kumbasar H (1999) Dipeptidyl peptidase IV and adenosine deaminase activity decrease in depression. Psychoneuroendocrinology 24(8):823–832PubMedCrossRefGoogle Scholar
  290. 290.
    Hildebrandt M et al (1999) Alterations in expression and in serum activity of dipeptidyl peptidase IV (DPP IV, CD26) in patients with hyporectic eating disorders. Scand J Immunol 50(5):536–541PubMedCrossRefGoogle Scholar
  291. 291.
    van West D et al (2000) Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa. Eur Arch Psychiatry Clin Neurosci 250(2):86–92PubMedCrossRefGoogle Scholar
  292. 292.
    Vlahović P et al (2007) Elevated serum dipeptidyl peptidase IV activity in patients with chronic tonsillitis. Ann Clin Biochem 44(1):70–74PubMedCrossRefGoogle Scholar
  293. 293.
    Gruss HJ et al (1997) Hodgkin’s disease: a tumor with disturbed immunological pathways. Immunol Today 18(4):156–163PubMedCrossRefGoogle Scholar
  294. 294.
    Chikuma T et al (1990) Purification and properties of dipeptidyl peptidase IV from human urine. Biol Chem Hoppe Seyler 371(4):325–330PubMedGoogle Scholar
  295. 295.
    Haacke W, Küllertz G, Barth A (1986) Diagnostic value of the enzyme dipeptidyl peptidase IV (DP IV) in abdominal cancers. Arch Geschwulstforsch 56(2):145–153PubMedGoogle Scholar
  296. 296.
    Küllertz G, Boigk J (1986) Dipeptidyl peptidase IV activity in the serum and synovia of patients with rheumatoid arthritis. Z Rheumatol 45(2):52–56PubMedGoogle Scholar
  297. 297.
    Elgün S et al (1999) Serum dipeptidyl peptidase IV activity correlates with the T-cell CD26 antigen. Clin Chem Lab Med 37(8):839–840PubMedCrossRefGoogle Scholar
  298. 298.
    Sedo A, Hátle K, Stolba P (1985) Changes in dipeptidyl-peptidase IV activity in human serum in pathological conditions of the thyroid gland. Cas Lek Cesk 124(51):1579–1581PubMedGoogle Scholar
  299. 299.
    Krepela E et al (1983) An assay of dipeptidyl peptidase IV activity in human serum and serum of pregnant women with glycyl-l-proline-1-naphthylamide and other glycyl-l-proline-arylamides as substrates. Physiol Bohemoslov 32(4):334–345PubMedGoogle Scholar
  300. 300.
    Bartles JR et al (1991) Decreases in the relative concentrations of specific hepatocyte plasma membrane proteins during liver regeneration: down-regulation or dilution? Dev Biol 143(2):258–270PubMedCrossRefGoogle Scholar
  301. 301.
    Bartles JR et al (1991) Expression and compartmentalization of integral plasma membrane proteins by hepatocytes and their progenitors in the rat pancreas. J Cell Sci 98(1):45–54PubMedGoogle Scholar
  302. 302.
    McCaughan GW et al (1990) Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: an analysis by tissue distribution, purification and N-terminal amino acid sequence. Hepatology 11(4):534–544PubMedCrossRefGoogle Scholar
  303. 303.
    McCaughan GW et al (2000) Molecular pathogenesis of liver disease: an approach to hepatic inflammation, cirrhosis and liver transplant tolerance. Immunol Rev 174:172–191PubMedCrossRefGoogle Scholar
  304. 304.
    O’Hara RJ et al (1998) Impaired interleukin-12 production is associated with a defective anti-tumour response in colorectal cancer. Dis Colon Rectum 41(4):460–463PubMedCrossRefGoogle Scholar
  305. 305.
    Cordero OJ et al (1997) Interleukin-12 enhances CD26 expression and dipeptidyl peptidase IV function on human activated lymphocytes. Immunobiology 197(5):522–533PubMedGoogle Scholar
  306. 306.
    Kasahara Y et al (1984) Glycylprolyl-diaminopeptidase in human leukocytes: selective occurrence in T lymphocytes and influence on the total serum enzyme activity. Clin Chim Acta 139(3):295–302PubMedCrossRefGoogle Scholar
  307. 307.
    Ward PE (1984) Immunoelectrophoretic analysis of vascular, membrane-bound angiotensin I converting enzyme, aminopeptidase M, and dipeptidyl(amino) peptidase IV. Biochem Pharmacol 33(20):3183–3193PubMedCrossRefGoogle Scholar
  308. 308.
    Mentzel S et al (1996) Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice. J Histochem Cytochem 44(5):445–461PubMedGoogle Scholar
  309. 309.
    Lojda Z (1979) Studies on dipeptidyl(amino)peptidase IV (glycyl-proline naphthylamidase). II. Blood vessels. Histochemistry 59(3):153–166PubMedCrossRefGoogle Scholar
  310. 310.
    van der Velden V et al (1998) Expression of aminopeptidase N and dipeptidyl peptidase IV in the healthy and asthmatic bronchus. Clin Exp Allergy 28(1):110–120PubMedCrossRefGoogle Scholar
  311. 311.
    Gossrau R (1979) Peptidases II. Localization of dipeptidylpeptidase IV (DPP IV). Histochemical and biochemical study. Histochemistry 60(2):231–248PubMedCrossRefGoogle Scholar
  312. 312.
    Sahara N et al (1983) Immunohistochemical localization of dipeptidyl peptidase IV in rat digestive organs. Acta Histochem Cytochem 16:494–501Google Scholar
  313. 313.
    Pala L et al (2003) Dipeptidyl peptidase-IV expression and activity in human glomerular endothelial cells. Biochem Biophys Res Commun 310(1):28–31PubMedCrossRefGoogle Scholar
  314. 314.
    Mavropoulos JC et al (2005) Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis. J Rheumatol 32(11):2116–2124PubMedGoogle Scholar
  315. 315.
    Uematsu T, Urade M, Yamaoka M (1998) Decreased expression and release of dipeptidyl peptidase IV (CD26) in cultured peripheral blood T lymphocytes of oral cancer patients. J Oral Pathol Med 27(3):106–110PubMedCrossRefGoogle Scholar
  316. 316.
    Uematsu T et al (2004) Effects of oral squamous cell carcinoma-derived TGF-beta1 on CD26/DPPIV expression in T cells. Anticancer Res 24(2B):619–624PubMedGoogle Scholar
  317. 317.
    Lojda Z (1981) Proteinases in pathology. Usefulness of histochemical methods. J Histochem Cytochem 29(3A Suppl):481–493PubMedGoogle Scholar
  318. 318.
    Lojda Z (1985) The importance of protease histochemistry in pathology. Histochem J 17(10):1063–1089PubMedCrossRefGoogle Scholar
  319. 319.
    Lojda Z (1988) Dipeptidyl peptidases of human lymphocytes. Czech Med 11(4):181–194PubMedGoogle Scholar
  320. 320.
    Sehmsdorf US et al (2004) Human miscarriage is associated with increased number of CD26 decidual lymphocytes. Scand J Immunol 59(4):400–407PubMedCrossRefGoogle Scholar
  321. 321.
    Scheel-Toellner D et al (1995) CD26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma. Lab Invest 73(5):685–690PubMedGoogle Scholar
  322. 322.
    Willheim M et al (1997) Cell surface characterization of T lymphocytes and allergen-specific T cell clones: correlation of CD26 expression with T(H1) subsets. J Allergy Clin Immunol 100(3):348–355PubMedCrossRefGoogle Scholar
  323. 323.
    Cavani A et al (2000) Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses. J Invest Dermatol 114(2):295–302PubMedCrossRefGoogle Scholar
  324. 324.
    Müller A et al (2000) Localized Wegener’s granulomatosis: predominance of CD26 and IFN-gamma expression. J Pathol 192(1):113–120PubMedCrossRefGoogle Scholar
  325. 325.
    Boonacker EP et al (2002) CD26/DPPIV signal transduction function, but not proteolytic activity, is directly related to its expression level on human Th1 and Th2 cell lines as detected with living cell cytochemistry. J Histochem Cytochem 50(9):1169–1177PubMedGoogle Scholar
  326. 326.
    Schade RP et al (2002) Cell-surface expression of CD25, CD26, and CD30 by allergen-specific T cells is intrinsically different in cow’s milk allergy. J Allergy Clin Immunol 109(2):357–362PubMedCrossRefGoogle Scholar
  327. 327.
    Nakao K et al (2002) Serum levels of soluble CD26 and CD30 in patients on hemodialysis. Nephron 91(2):215–221PubMedCrossRefGoogle Scholar
  328. 328.
    Fierro MT et al (2006) Expression pattern of chemokine receptors and chemokine release in inflammatory erythroderma and Sézary syndrome. Dermatology 213(4):284–292PubMedCrossRefGoogle Scholar
  329. 329.
    Krakauer M, Sorensen PS, Sellebjerg F (2006) CD4(+) memory T cells with high CD26 surface expression are enriched for Th1 markers and correlate with clinical severity of multiple sclerosis. J Neuroimmunol 181(1–2):157–164PubMedCrossRefGoogle Scholar
  330. 330.
    Jafari-Shakib R et al (2008) CD26 expression on CD4+ T cells in patients with cutaneous leishmaniasis. Clin Exp Immunol 153(1):31–36PubMedCrossRefGoogle Scholar
  331. 331.
    Ilhan F et al (2008) Th1 polarization of the immune response in uveitis in Behçet’s disease. Can J Ophthalmol 43(1):105–108PubMedCrossRefGoogle Scholar
  332. 332.
    Ma Y et al (2008) The CD4+ CD26− T-cell population in classical Hodgkin’s lymphoma displays a distinctive regulatory T-cell profile. Lab Invest 88(5):482–490PubMedCrossRefGoogle Scholar
  333. 333.
    Cordon-Cardo C, Prives C (1999) At the crossroads of inflammation and tumorigenesis. J Exp Med 190(10):1367–1370PubMedCrossRefGoogle Scholar
  334. 334.
    Dvorak-HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659PubMedCrossRefGoogle Scholar
  335. 335.
    Strieter RM et al (2004) CXC chemokines: angiogenesis, immunoangiostasis, and metastases in lung cancer. Ann N Y Acad Sci 1028(12):351–360PubMedCrossRefGoogle Scholar
  336. 336.
    Szlosarek PW, Balkwill FR (2003) Tumour necrosis factor alpha: a potential target for the therapy of solid tumours. Lancet Oncol 4(9):565–573PubMedCrossRefGoogle Scholar
  337. 337.
    Byrd JB et al (2007) Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema. J Allergy Clin Immunol 120(2):403–408PubMedCrossRefGoogle Scholar
  338. 338.
    Waldmann TA (2006) Effective cancer therapy through immunomodulation. Annu Rev Med 57:65–81PubMedCrossRefGoogle Scholar
  339. 339.
    Zou W et al (2001) Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 7(12):1339–1346PubMedCrossRefGoogle Scholar
  340. 340.
    Hartmann E et al (2003) Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res 63(19):6478–6487PubMedGoogle Scholar
  341. 341.
    Curiel TJ et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949PubMedCrossRefGoogle Scholar
  342. 342.
    Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131(11 Suppl):3109–3120Google Scholar
  343. 343.
    Masur K et al (2006) DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells. Regul Pept 137(3):147–155PubMedCrossRefGoogle Scholar
  344. 344.
    Lenhard JM, Croom DK, Minnick DT (2004) Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments. Biochem Biophys Res Commun 324(1):92–97PubMedCrossRefGoogle Scholar
  345. 345.
    Wang CH et al (2008) Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system. Am J Physiol Regul Integr Comp Physiol 294(3):R811–R818PubMedGoogle Scholar
  346. 346.
    Dang DT et al (2008) Hypoxia-inducible factor-1 target genes as indicators of tumor vessel response to vascular endothelial growth factor inhibition. Cancer Res 68(6):1872–1880PubMedCrossRefGoogle Scholar
  347. 347.
    Ghersi G et al (2001) Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial cell migration in response to wounding. Peptides 22(3):453–458PubMedCrossRefGoogle Scholar
  348. 348.
    Thompson JA et al (2008) Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma. J Clin Oncol 26(12):2034–2039PubMedCrossRefGoogle Scholar
  349. 349.
    Dougan M, Dranoff G (2009) Immune therapy for cancer. Annu Rev Immunol 27:83–117PubMedCrossRefGoogle Scholar
  350. 350.
    Rolle CE, Carrio R, Malek TR (2008) Modeling the CD8+ T effector to memory transition in adoptive T-cell antitumor immunotherapy. Cancer Res 68(8):2984–2992PubMedCrossRefGoogle Scholar
  351. 351.
    Duan X et al (2009) Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors. Cancer 115(1):13–22PubMedCrossRefGoogle Scholar
  352. 352.
    Park S, Cheon S, Cho D (2007) The dual effects of interleukin-18 in tumor progression. Cell Mol Immunol 4(5):329–335PubMedGoogle Scholar
  353. 353.
    Mocellin S, Nitti D (2008) TNF and cancer: the two sides of the coin. Front Biosci 13:2774–2783PubMedCrossRefGoogle Scholar
  354. 354.
    Mocellin S et al (2005) Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev 16(1):35–53PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Oscar J. Cordero
    • 1
    Email author
  • Francisco J. Salgado
    • 1
  • Montserrat Nogueira
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, CIBUSUniversity of Santiago de CompostelaSantiago de CompostelaSpain

Personalised recommendations