Annals of Hematology

, Volume 90, Issue 5, pp 493–508 | Cite as

CD44 in hematological neoplasias

  • Magdalena Katharina Hertweck
  • Felix Erdfelder
  • Karl-Anton Kreuzer
Review Article


The CD44 protein family spans a large group of transmembrane glycoproteins acquired by alternative splicing and post-translational modifications. The great heterogeneity in molecular structure is reflected in its various important functions: CD44 mediates (1) interaction between cell and extracellular matrix, (2) signal submission, e.g., by acting as co-receptor for membrane-spanning receptor tyrosine kinases or by association with intracellular molecules initiating several signaling pathways, and (3) anchor function connecting to the cytoskeleton via the ezrin-radixin-moesin protein family. The expression pattern of the different CD44 isoforms display strong variations dependent on cell type, state of activation, and differentiation stage. In hematopoietic cells, CD44 mediates interaction of progenitor cells and bone marrow stroma during hematopoiesis, regulates maturation, and activation-induced cell death in T cells, influences neutrophil and macrophage migration as well as cytokine production, and participates in lymphocyte extravasation and migration. CD44 is involved in development and progress of hematological neoplasias by enhancement of apoptotic resistance, invasiveness, as well as regulation of bone marrow homing, and mobilization of leukemia-initiating cells into the peripheral blood. Thereby altered CD44 expression functions as marker for worse prognosis in most hematological malignancies. Additionally, CD44 expression levels can be used to distinguish between different hematological neoplasias and subtypes. Concerning new treatment strategies, CD44 displays promising potential either by direct targeting of CD44 expressed on the malignant cells or reversing an acquired resistance to primary treatment mediated through altered CD44 expression. The former can be achieved by antibody or hyaluronan-based immunotherapy.


CD44 Hematological malignancies CD44 antibody Hyaluronan 


  1. 1.
    Dalchau R, Kirkley J, Fabre JW (1980) Monoclonal antibody to a human leukocyte-specific membrane glycoprotein probably homologous to the leukocyte-common (L-C) antigen of the rat. Eur J Immunol 10(10):737–744PubMedCrossRefGoogle Scholar
  2. 2.
    Ponta H, Wainwright D, Herrlich P (1998) The CD44 protein family. Int J Biochem Cell Biol 30(3):299–305PubMedCrossRefGoogle Scholar
  3. 3.
    Screaton GR, Bell MV, Jackson DG, Cornelis FB, Gerth U, Bell JI (1992) Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A 89(24):12160–12164PubMedCrossRefGoogle Scholar
  4. 4.
    Günthert U (1993) CD44: a multitude of isoforms with diverse functions. Curr Top Microbiol Immunol 184:47–63PubMedGoogle Scholar
  5. 5.
    Naor D, Wallach-Dayan SB, Zahalka MA, Sionov RV (2008) Involvement of CD44, a molecule with a thousand faces, in cancer dissemination. Semin Cancer Biol 18(4):260–267PubMedCrossRefGoogle Scholar
  6. 6.
    Fichter M, Hinrichs R, Eissner G, Scheffer B, Classen S, Ueffing M (1997) Expression of CD44 isoforms in neuroblastoma cells is regulated by PI 3-kinase and protein kinase C. Oncogene 14(23):2817–2824PubMedCrossRefGoogle Scholar
  7. 7.
    Fitzgerald KA, O'Neill LA (1999) Characterization of CD44 induction by IL-1: a critical role for Egr-1. J Immunol 162(8):4920–4927PubMedGoogle Scholar
  8. 8.
    König H, Ponta H, Herrlich P (1998) Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator. EMBO J 17(10):2904–2913PubMedCrossRefGoogle Scholar
  9. 9.
    Khan SA, Cook AC, Kappil M, Günthert U, Chambers AF, Tuck AB, Denhardt DT (2005) Enhanced cell surface CD44 variant (v6, v9) expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration: novel post-transcriptional, post-translational regulation. Clin Exp Metastasis 22(8):663–673PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang T, Huang X, Dong L, Hu D, Ge C, Zhan Y, Xu W, Yu M, Li W et al (2010) PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells. Mol Cancer 9:72PubMedCrossRefGoogle Scholar
  11. 11.
    Yan C, Wu W, Li H, Zhang G, Duerksen-Hughes PJ, Zhu X, Yang J (2010) Benzo[a]pyrene treatment leads to changes in nuclear protein expression and alternative splicing. Mutat Res 686(1–2):47–56PubMedGoogle Scholar
  12. 12.
    Naor D, Sionov RV, Ish-Shalom D (1997) CD44: structure, function, and association with the malignant process. Adv Cancer Res 71:241–319PubMedCrossRefGoogle Scholar
  13. 13.
    Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4(1):33–45PubMedCrossRefGoogle Scholar
  14. 14.
    Mori T, Kitano K, Terawaki S, Maesaki R, Fukami Y, Hakoshima T (2008) Structural basis for CD44 recognition by ERM proteins. J Biol Chem 283(43):29602–29612PubMedCrossRefGoogle Scholar
  15. 15.
    Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H, Seiki M (2001) Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153(5):893–904PubMedCrossRefGoogle Scholar
  16. 16.
    Cichy J, Puré E (2004) Cytokines regulate the affinity of soluble CD44 for hyaluronan. FEBS Lett 556(1–3):69–74PubMedCrossRefGoogle Scholar
  17. 17.
    Murai T, Miyauchi T, Yanagida T, Sako Y (2006) Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10. Biochem J 395(1):65–71PubMedCrossRefGoogle Scholar
  18. 18.
    Mackay CR, Terpe HJ, Stauder R, Marston WL, Stark H, Günthert U (1994) Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 124(1–2):71–82PubMedCrossRefGoogle Scholar
  19. 19.
    Legras S, Günthert U, Stauder R, Curt F, Oliferenko S, Kluin-Nelemans HC, Marie JP, Proctor S, Jasmin C et al (1998) A strong expression of CD44-6v correlates with shorter survival of patients with acute myeloid leukemia. Blood 91(9):3401–3413PubMedGoogle Scholar
  20. 20.
    Günthert U, Hofmann M, Rudy W, Reber S, Zöller M, Haussmann I, Matzku S, Wenzel A, Ponta H et al (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65(1):13–24PubMedCrossRefGoogle Scholar
  21. 21.
    Heider K, Kuthan H, Stehle G, Munzert G (2004) CD44v6: a target for antibody-based cancer therapy. Cancer Immunol Immunother 53(7):567–579PubMedCrossRefGoogle Scholar
  22. 22.
    Kai K, Arima Y, Kamiya T, Saya H (2010) Breast cancer stem cells. Breast Cancer 17(2):80–85PubMedCrossRefGoogle Scholar
  23. 23.
    Todaro M, Francipane MG, Medema JP, Stassi G (2010) Colon cancer stem cells: promise of targeted therapy. Gastroenterology 138(6):2151–2162PubMedCrossRefGoogle Scholar
  24. 24.
    Lee CJ, Dosch J, Simeone DM (2008) Pancreatic cancer stem cells. J Clin Oncol 26(17):2806–2812PubMedCrossRefGoogle Scholar
  25. 25.
    Zou G (2010) Liver cancer stem cells as an important target in liver cancer therapies. Anticancer Agents Med Chem 10(2):172–175PubMedGoogle Scholar
  26. 26.
    Perschl A, Lesley J, English N, Trowbridge I, Hyman R (1995) Role of CD44 cytoplasmic domain in hyaluronan binding. Eur J Immunol 25(2):495–501PubMedCrossRefGoogle Scholar
  27. 27.
    Cichy J, Pure E (2000) Oncostatin M and transforming growth factor-beta 1 induce post-translational modification and hyaluronan binding to CD44 in lung-derived epithelial tumor cells. J Biol Chem 275(24):18061–18069PubMedCrossRefGoogle Scholar
  28. 28.
    Katoh S, Zheng Z, Oritani K, Shimozato T, Kincade PW (1995) Glycosylation of CD44 negatively regulates its recognition of hyaluronan. J Exp Med 182(2):419–429PubMedCrossRefGoogle Scholar
  29. 29.
    Puré E, Assoian RK (2009) Rheostatic signaling by CD44 and hyaluronan. Cell Signal 21(5):651–655PubMedCrossRefGoogle Scholar
  30. 30.
    Fujiwara T, Kawakatsu T, Tayama S, Kobayashi Y, Sugiura N, Kimata K, Takai Y (2008) Hyaluronan-CD44 pathway regulates orientation of mitotic spindle in normal epithelial cells. Genes Cells 13(7):759–770PubMedCrossRefGoogle Scholar
  31. 31.
    Legras S, Levesque JP, Charrad R, Morimoto K, Le Bousse C, Clay D, Jasmin C, Smadja-Joffe F (1997) CD44-mediated adhesiveness of human hematopoietic progenitors to hyaluronan is modulated by cytokines. Blood 89(6):1905–1914PubMedGoogle Scholar
  32. 32.
    Levesque MC, Haynes BF (1999) TNFalpha and IL-4 regulation of hyaluronan binding to monocyte CD44 involves posttranslational modification of CD44. Cell Immunol 193(2):209–218PubMedCrossRefGoogle Scholar
  33. 33.
    Brown KL, Maiti A, Johnson P (2001) Role of sulfation in CD44-mediated hyaluronan binding induced by inflammatory mediators in human CD14(+) peripheral blood monocytes. J Immunol 167(9):5367–5374PubMedGoogle Scholar
  34. 34.
    DeGrendele HC, Kosfiszer M, Estess P, Siegelman MH (1997) CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation. J Immunol 159(6):2549–2553PubMedGoogle Scholar
  35. 35.
    Verfaillie CM, Benis A, Iida J, McGlave PB, McCarthy JB (1994) Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin alpha 4 beta 1 and the CD44 adhesion receptor. Blood 84(6):1802–1811PubMedGoogle Scholar
  36. 36.
    Nandi A, Estess P, Siegelman M (2004) Bimolecular complex between rolling and firm adhesion receptors required for cell arrest; CD44 association with VLA-4 in T cell extravasation. Immunity 20(4):455–465PubMedCrossRefGoogle Scholar
  37. 37.
    Lee J, Wang M, Sudhir P, Chen G, Chi C, Chen J (2007) Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN–CD44V interaction enhances survival in gastrointestinal cancer cells. Cancer Res 67(5):2089–2097PubMedCrossRefGoogle Scholar
  38. 38.
    Wang H, Hung Y, Su C, Peng S, Guo Y, Lai M, Liu C, Hsu J (2005) CD44 cross-linking induces integrin-mediated adhesion and transendothelial migration in breast cancer cell line by up-regulation of LFA-1 (alpha L beta2) and VLA-4 (alpha4beta1). Exp Cell Res 304(1):116–126PubMedCrossRefGoogle Scholar
  39. 39.
    Torre C, Wang SJ, Xia W, Bourguignon LYW (2010) Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling. Arch Otolaryngol Head Neck Surg 136(5):493–501PubMedCrossRefGoogle Scholar
  40. 40.
    Baronas-Lowell D, Lauer-Fields JL, Borgia JA, Sferrazza GF, Al-Ghoul M, Minond D, Fields GB (2004) Differential modulation of human melanoma cell metalloproteinase expression by alpha2beta1 integrin and CD44 triple-helical ligands derived from type IV collagen. J Biol Chem 279(42):43503–43513PubMedCrossRefGoogle Scholar
  41. 41.
    Yu Q, Stamenkovic I (1999) Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev 13(1):35–48PubMedCrossRefGoogle Scholar
  42. 42.
    Lefebvre DC, Lai JCY, Maeshima N, Ford JL, Wong ASL, Cross JL, Johnson P (2010) CD44 interacts directly with Lck in a zinc-dependent manner. Mol Immunol 47(10):1882–1889PubMedCrossRefGoogle Scholar
  43. 43.
    Bourguignon LY, Zhu H, Shao L, Chen YW (2001) CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. J Biol Chem 276(10):7327–7336PubMedCrossRefGoogle Scholar
  44. 44.
    Ilangumaran S, Arni S, van Echten-Deckert G, Borisch B, Hoessli DC (1999) Microdomain-dependent regulation of Lck and Fyn protein-tyrosine kinases in T lymphocyte plasma membranes. Mol Biol Cell 10(4):891–905PubMedGoogle Scholar
  45. 45.
    McClatchey AI (2003) Merlin and ERM proteins: unappreciated roles in cancer development? Nat Rev Cancer 3(11):877–883PubMedCrossRefGoogle Scholar
  46. 46.
    Terawaki S, Kitano K, Mori T, Zhai Y, Higuchi Y, Itoh N, Watanabe T, Kaibuchi K, Hakoshima T (2010) The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. EMBO J 29(1):236–250PubMedCrossRefGoogle Scholar
  47. 47.
    Wang KX, Denhardt DT (2008) Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 19(5–6):333–345PubMedCrossRefGoogle Scholar
  48. 48.
    Tanikawa R, Tanikawa T, Hirashima M, Yamauchi A, Tanaka Y (2010) Galectin-9 induces osteoblast differentiation through the CD44/Smad signaling pathway. Biochem Biophys Res Commun 394(2):317–322PubMedCrossRefGoogle Scholar
  49. 49.
    Peterson RS, Andhare RA, Rousche KT, Knudson W, Wang W, Grossfield JB, Thomas RO, Hollingsworth RE, Knudson CB (2004) CD44 modulates Smad1 activation in the BMP-7 signaling pathway. J Cell Biol 166(7):1081–1091PubMedCrossRefGoogle Scholar
  50. 50.
    Bourguignon LYW, Wong G, Earle C, Krueger K, Spevak CC (2010) Hyaluronan-CD44 interaction promotes c-Src-mediated twist signaling, MicroRNA-10b expression and RhoA/RhoC upregulation leading to Rho-kinase-associated cytoskeleton activation and breast tumor cell invasion. J Biol Chem 285(47):36721–36735PubMedCrossRefGoogle Scholar
  51. 51.
    Bretscher A, Edwards K, Fehon RG (2002) ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 3(8):586–599PubMedCrossRefGoogle Scholar
  52. 52.
    Turley EA, Noble PW, Bourguignon LYW (2002) Signaling properties of hyaluronan receptors. J Biol Chem 277(7):4589–4592PubMedCrossRefGoogle Scholar
  53. 53.
    Yu Q, Stamenkovic I (2004) Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival. Clin Exp Metastasis 21(3):235–242PubMedCrossRefGoogle Scholar
  54. 54.
    Tian Y, Phillips AO (2003) TGF-beta1-mediated inhibition of HK-2 cell migration. J Am Soc Nephrol 14(3):631–640PubMedCrossRefGoogle Scholar
  55. 55.
    Oliferenko S, Kaverina I, Small JV, Huber LA (2000) Hyaluronic acid (HA) binding to CD44 activates Rac1 and induces lamellipodia outgrowth. J Cell Biol 148(6):1159–1164PubMedCrossRefGoogle Scholar
  56. 56.
    Subramaniam V, Vincent IR, Gardner H, Chan E, Dhamko H, Jothy S (2007) CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation. Exp Mol Pathol 83(2):207–215PubMedCrossRefGoogle Scholar
  57. 57.
    Shi X, Leng L, Wang T, Wang W, Du X, Li J, McDonald C, Chen Z, Murphy JW et al (2006) CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity 25(4):595–606PubMedCrossRefGoogle Scholar
  58. 58.
    Mielgo A, Brondani V, Landmann L, Glaser-Ruhm A, Erb P, Stupack D, Günthert U (2007) The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells. Apoptosis 12(11):2051–2061PubMedCrossRefGoogle Scholar
  59. 59.
    Okamoto I, Kawano Y, Murakami D, Sasayama T, Araki N, Miki T, Wong AJ, Saya H (2001) Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway. J Cell Biol 155(5):755–762PubMedCrossRefGoogle Scholar
  60. 60.
    Kim Y, Lee Y, Choe J, Lee H, Kim Y, Jeoung D (2008) CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2. J Biol Chem 283(33):22513–22528PubMedCrossRefGoogle Scholar
  61. 61.
    Puré E, Cuff CA (2001) A crucial role for CD44 in inflammation. Trends Mol Med 7(5):213–221PubMedCrossRefGoogle Scholar
  62. 62.
    Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106(6):1901–1910PubMedCrossRefGoogle Scholar
  63. 63.
    Ohata S, Nawa M, Kasama T, Yamasaki T, Sawanobori K, Hata S, Nakamura T, Asaoka Y, Watanabe T et al (2009) Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells. Biochem Biophys Res Commun 379(4):817–823PubMedCrossRefGoogle Scholar
  64. 64.
    Chen K, Liu J, Heck S, Chasis JA, An X, Mohandas N (2009) Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis. Proc Natl Acad Sci U S A 106(41):17413–17418PubMedCrossRefGoogle Scholar
  65. 65.
    Vaskova M, Fronkova E, Starkova J, Kalina T, Mejstrikova E, Hrusak O (2008) CD44 and CD27 delineate B-precursor stages with different recombination status and with an uneven distribution in nonmalignant and malignant hematopoiesis. Tissue Antigens 71(1):57–66PubMedGoogle Scholar
  66. 66.
    Rajasagi M, Vitacolonna M, Benjak B, Marhaba R, Zöller M (2009) CD44 promotes progenitor homing into the thymus and T cell maturation. J Leukoc Biol 85(2):251–261PubMedCrossRefGoogle Scholar
  67. 67.
    Baaten BJG, Li C, Deiro MF, Lin MM, Linton PJ, Bradley LM (2010) CD44 regulates survival and memory development in Th1 cells. Immunity 32(1):104–115PubMedCrossRefGoogle Scholar
  68. 68.
    Nakano K, Saito K, Mine S, Matsushita S, Tanaka Y (2007) Engagement of CD44 up-regulates Fas ligand expression on T cells leading to activation-induced cell death. Apoptosis 12(1):45–54PubMedCrossRefGoogle Scholar
  69. 69.
    Ruffell B, Johnson P (2008) Hyaluronan induces cell death in activated T cells through CD44. J Immunol 181(10):7044–7054PubMedGoogle Scholar
  70. 70.
    Ogino S, Nishida N, Umemoto R, Suzuki M, Takeda M, Terasawa H, Kitayama J, Matsumoto M, Hayasaka H et al (2010) Two-state conformations in the hyaluronan-binding domain regulate CD44 adhesiveness under flow condition. Structure 18(5):649–656PubMedCrossRefGoogle Scholar
  71. 71.
    Napier SL, Healy ZR, Schnaar RL, Konstantopoulos K (2007) Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands. J Biol Chem 282(6):3433–3441PubMedCrossRefGoogle Scholar
  72. 72.
    Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch CAG, Sodek J (2004) Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors: evidence of a role for an intracellular form of osteopontin. J Cell Physiol 198(1):155–167PubMedCrossRefGoogle Scholar
  73. 73.
    Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ et al (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287(5454):860–864PubMedCrossRefGoogle Scholar
  74. 74.
    Muto J, Yamasaki K, Taylor KR, Gallo RL (2009) Engagement of CD44 by hyaluronan suppresses TLR4 signaling and the septic response to LPS. Mol Immunol 47(2–3):449–456PubMedCrossRefGoogle Scholar
  75. 75.
    Hoffmann U, Heilmann K, Hayford C, Stallmach A, Wahnschaffe U, Zeitz M, Günthert U, Wittig BM (2007) CD44v7 ligation downregulates the inflammatory immune response in Crohn's disease patients by apoptosis induction in mononuclear cells from the lamina propria. Cell Death Differ 14(8):1542–1551PubMedCrossRefGoogle Scholar
  76. 76.
    McKee CM, Penno MB, Cowman M, Burdick MD, Strieter RM, Bao C, Noble PW (1996) Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. J Clin Invest 98(10):2403–2413PubMedCrossRefGoogle Scholar
  77. 77.
    Alstergren P, Zhu B, Glogauer M, Glougauer M, Mak TW, Ellen RP, Sodek J (2004) Polarization and directed migration of murine neutrophils is dependent on cell surface expression of CD44. Cell Immunol 231(1–2):146–157PubMedCrossRefGoogle Scholar
  78. 78.
    Takazoe K, Tesch GH, Hill PA, Hurst LA, Jun Z, Lan HY, Atkins RC, Nikolic-Paterson DJ (2000) CD44-mediated neutrophil apoptosis in the rat. Kidney Int 58(5):1920–1930PubMedCrossRefGoogle Scholar
  79. 79.
    Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, Kon S, Maeda M, Hotta H et al (2001) Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes. J Exp Med 194(9):1219–1229PubMedCrossRefGoogle Scholar
  80. 80.
    Takano H, Nakazawa S, Shirata N, Tamba S, Furuta K, Tsuchiya S, Morimoto K, Itano N, Irie A et al (2009) Involvement of CD44 in mast cell proliferation during terminal differentiation. Lab Invest 89(4):446–455PubMedCrossRefGoogle Scholar
  81. 81.
    Magyarosy E, Sebestyén A, Timár J (2001) Expression of metastasis associated proteins, CD44v6 and NM23-H1, in pediatric acute lymphoblastic leukemia. Anticancer Res 21(1B):819–823PubMedGoogle Scholar
  82. 82.
    Bendall LJ, Nilsson SK, Khan NI, James A, Bonnet C, Lock RB, Papa R, Bradstock KF, Gottlieb DJ (2004) Role of CD44 variant exon 6 in acute lymphoblastic leukaemia: association with altered bone marrow localisation and increased tumour burden. Leukemia 18(7):1308–1311PubMedCrossRefGoogle Scholar
  83. 83.
    Khan NI, Cisterne A, Devidas M, Shuster J, Hunger SP, Shaw PJ, Bradstock KF, Bendall LJ (2008) Expression of CD44, but not CD44v6, predicts relapse in children with B cell progenitor acute lymphoblastic leukemia lacking adverse or favorable genetics. Leuk Lymphoma 49(4):710–718PubMedCrossRefGoogle Scholar
  84. 84.
    Vaskova M, Mejstrikova E, Kalina T, Martinkova P, Omelka M, Trka J, Stary J, Hrusak O (2005) Transfer of genomics information to flow cytometry: expression of CD27 and CD44 discriminates subtypes of acute lymphoblastic leukemia. Leukemia 19(5):876–878PubMedCrossRefGoogle Scholar
  85. 85.
    Charrad RS, Li Y, Delpech B, Balitrand N, Clay D, Jasmin C, Chomienne C, Smadja-Joffe F (1999) Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia. Nat Med 5(6):669–676PubMedCrossRefGoogle Scholar
  86. 86.
    Charrad R, Gadhoum Z, Qi J, Glachant A, Allouche M, Jasmin C, Chomienne C, Smadja-Joffe F (2002) Effects of anti-CD44 monoclonal antibodies on differentiation and apoptosis of human myeloid leukemia cell lines. Blood 99(1):290–299PubMedCrossRefGoogle Scholar
  87. 87.
    Song G, Liao X, Zhou L, Wu L, Feng Y, Han ZC (2004) HI44a, an anti-CD44 monoclonal antibody, induces differentiation and apoptosis of human acute myeloid leukemia cells. Leuk Res 28(10):1089–1096PubMedCrossRefGoogle Scholar
  88. 88.
    Bourcier S, Sansonetti A, Durand L, Chomienne C, Robert-Lézénés J, Smadja-Joffe F (2010) CD44-ligation induces, through ERK1/2 pathway, synthesis of cytokines TNF-alpha and IL-6 required for differentiation of THP-1 monoblastic leukemia cells. Leukemia 24(7):1372–1375PubMedCrossRefGoogle Scholar
  89. 89.
    Delaunay J, Lecomte N, Bourcier S, Qi J, Gadhoum Z, Durand L, Chomienne C, Robert-Lézénès J, Smadja-Joffe F (2008) Contribution of GM-CSF and IL-8 to the CD44-induced differentiation of acute monoblastic leukemia. Leukemia 22(4):873–876PubMedCrossRefGoogle Scholar
  90. 90.
    Nervi B, Link DC, DiPersio JF (2006) Cytokines and hematopoietic stem cell mobilization. J Cell Biochem 99(3):690–705PubMedCrossRefGoogle Scholar
  91. 91.
    Telen MJ (2005) Erythrocyte adhesion receptors: blood group antigens and related molecules. Transfus Med Rev 19(1):32–44PubMedCrossRefGoogle Scholar
  92. 92.
    Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12(10):1167–1174PubMedCrossRefGoogle Scholar
  93. 93.
    Funayama K, Shimane M, Nomura H, Asano S (2010) An evidence for adhesion-mediated acquisition of acute myeloid leukemic stem cell-like immaturities. Biochem Biophys Res Commun 392(3):271–276PubMedCrossRefGoogle Scholar
  94. 94.
    Abecassis I, Maes J, Carrier J, Hillion J, Goodhardt M, Medjber K, Wany L, Lanotte M, Karniguian A (2008) Re-expression of DNA methylation-silenced CD44 gene in a resistant NB4 cell line: rescue of CD44-dependent cell death by cAMP. Leukemia 22(3):511–520PubMedCrossRefGoogle Scholar
  95. 95.
    Peterson LF, Wang Y, Lo M, Yan M, Kanbe E, Zhang D (2007) The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation. Leukemia 21(9):2010–2019PubMedCrossRefGoogle Scholar
  96. 96.
    Attarbaschi A, Mann G, Schumich A, König M, Pickl WF, Haas OA, Gadner H, Dworzak MN (2007) CD44 deficiency is a consistent finding in childhood Burkitt's lymphoma and leukemia. Leukemia 21(5):1110–1113PubMedCrossRefGoogle Scholar
  97. 97.
    Rodig SJ, Vergilio J, Shahsafaei A, Dorfman DM (2008) Characteristic expression patterns of TCL1, CD38, and CD44 identify aggressive lymphomas harboring a MYC translocation. Am J Surg Pathol 32(1):113–122PubMedCrossRefGoogle Scholar
  98. 98.
    Schniederjan SD, Li S, Saxe DF, Lechowicz MJ, Lee KL, Terry PD, Mann KP (2010) A novel flow cytometric antibody panel for distinguishing Burkitt lymphoma from CD10+ diffuse large B-cell lymphoma. Am J Clin Pathol 133(5):718–726PubMedCrossRefGoogle Scholar
  99. 99.
    Stauder R, Eisterer W, Thaler J, Günthert U (1995) CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor. Blood 85(10):2885–2899PubMedGoogle Scholar
  100. 100.
    Ristamäki R, Joensuu H, Söderström KO, Jalkanen S (1995) CD44v6 expression in non-Hodgkin's lymphoma: an association with low histological grade and poor prognosis. J Pathol 176(3):259–267PubMedCrossRefGoogle Scholar
  101. 101.
    Drillenburg P, Wielenga VJ, Kramer MH, van Krieken JH, Kluin-Nelemans HC, Hermans J, Heisterkamp S, Noordijk EM, Kluin PM (1999) CD44 expression predicts disease outcome in localized large B cell lymphoma. Leukemia 13(9):1448–1455PubMedCrossRefGoogle Scholar
  102. 102.
    Inagaki H, Banno S, Wakita A, Ueda R, Eimoto T (1999) Prognostic significance of CD44v6 in diffuse large B-cell lymphoma. Mod Pathol 12(5):546–552PubMedGoogle Scholar
  103. 103.
    Tzankov A, Pehrs A, Zimpfer A, Ascani S, Lugli A, Pileri S, Dirnhofer S (2003) Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases. J Clin Pathol 56(10):747–752PubMedCrossRefGoogle Scholar
  104. 104.
    Hu X, Chen Y, Liang ACT, Au W, Wong K, Wan TSK, Wong MLY, Shen L, Chan K et al (2010) CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation. Blood 115(12):2458–2461PubMedCrossRefGoogle Scholar
  105. 105.
    Zarcone D, De Rossi G, Tenca C, Marroni P, Mauro FR, Cerruti GM, Albi N, Fiorucci S, Velardi A et al (1998) Functional and clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia cells. Haematologica 83(12):1088–1098PubMedGoogle Scholar
  106. 106.
    Bairey O, Zimra Y, Rabizadeh E, Shaklai M (2004) Expression of adhesion molecules on leukemic B cells from chronic lymphocytic leukemia patients with predominantly splenic manifestations. Isr Med Assoc J 6(3):147–151PubMedGoogle Scholar
  107. 107.
    Molica S, Vitelli G, Levato D, Giannarelli D, Gandolfo GM (2001) Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression. Cancer 92(4):713–719PubMedCrossRefGoogle Scholar
  108. 108.
    Eisterer W, Bechter O, Söderberg O, Nilsson K, Terol M, Greil R, Thaler J, Herold M, Finke L et al (2004) Elevated levels of soluble CD44 are associated with advanced disease and in vitro proliferation of neoplastic lymphocytes in B-cell chronic lymphocytic leukaemia. Leuk Res 28(10):1043–1051PubMedCrossRefGoogle Scholar
  109. 109.
    Pedersen IM, Kitada S, Leoni LM, Zapata JM, Karras JG, Tsukada N, Kipps TJ, Choi YS, Bennett F et al (2002) Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1. Blood 100(5):1795–1801PubMedGoogle Scholar
  110. 110.
    Redondo-Muñoz J, Ugarte-Berzal E, García-Marco JA, del Cerro MH, Van den Steen PE, Opdenakker G, Terol MJ, García-Pardo A (2008) Alpha4beta1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells. Blood 112(1):169–178PubMedCrossRefGoogle Scholar
  111. 111.
    Kim I, Uchiyama H, Chauhan D, Anderson KC (1994) Cell surface expression and functional significance of adhesion molecules on human myeloma-derived cell lines. Br J Haematol 87(3):483–493PubMedCrossRefGoogle Scholar
  112. 112.
    Van Driel M, Günthert U, van Kessel AC, Joling P, Stauder R, Lokhorst HM, Bloem AC (2002) CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells. Leukemia 16(1):135–143PubMedCrossRefGoogle Scholar
  113. 113.
    Asosingh K, Günthert U, Bakkus MH, De Raeve H, Goes E, Van Riet I, Van Camp B, Vanderkerken K (2000) In vivo induction of insulin-like growth factor-I receptor and CD44v6 confers homing and adhesion to murine multiple myeloma cells. Cancer Res 60(11):3096–3104PubMedGoogle Scholar
  114. 114.
    Caers J, Günthert U, De Raeve H, Van Valckenborgh E, Menu E, Van Riet I, Van Camp B, Vanderkerken K (2006) The involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model. Br J Haematol 132(4):469–477PubMedGoogle Scholar
  115. 115.
    Stauder R, Van Driel M, Schwärzler C, Thaler J, Lokhorst HM, Kreuser ED, Bloem AC, Günthert U, Eisterer W (1996) Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. Blood 88(8):3101–3108PubMedGoogle Scholar
  116. 116.
    Eisterer W, Bechter O, Hilbe W, van Driel M, Lokhorst HM, Thaler J, Bloem AC, Günthert U, Stauder R (2001) CD44 isoforms are differentially regulated in plasma cell dyscrasias and CD44v9 represents a new independent prognostic parameter in multiple myeloma. Leuk Res 25(12):1051–1057PubMedCrossRefGoogle Scholar
  117. 117.
    Liebisch P, Eppinger S, Schöpflin C, Stehle G, Munzert G, Döhner H, Schmid M (2005) CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q. Haematologica 90(4):489–493PubMedGoogle Scholar
  118. 118.
    Ma Y, Visser L, Roelofsen H, de Vries M, Diepstra A, van Imhoff G, van der Wal T, Luinge M, Alvarez-Llamas G et al (2008) Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes. Blood 111(4):2339–2346PubMedCrossRefGoogle Scholar
  119. 119.
    Kim Y, Seo D, Kong S, Lee J, Lee E, Stetler-Stevenson M, Stetler-Stevenson WG (2008) TIMP1 induces CD44 expression and the activation and nuclear translocation of SHP1 during the late centrocyte/post-germinal center B cell differentiation. Cancer Lett 269(1):37–45PubMedCrossRefGoogle Scholar
  120. 120.
    Beham-Schmid C, Heider KH, Hoefler G, Zatloukal K (1998) Expression of CD44 splice variant v10 in Hodgkin's disease is associated with aggressive behaviour and high risk of relapse. J Pathol 186(4):383–389PubMedCrossRefGoogle Scholar
  121. 121.
    Heider KH, Sproll M, Susani S, Patzelt E, Beaumier P, Ostermann E, Ahorn H, Adolf GR (1996) Characterization of a high-affinity monoclonal antibody specific for CD44v6 as candidate for immunotherapy of squamous cell carcinomas. Cancer Immunol Immunother 43(4):245–253PubMedCrossRefGoogle Scholar
  122. 122.
    Börjesson PKE, Postema EJ, Roos JC, Colnot DR, Marres HAM, van Schie MH, Stehle G, de Bree R, Snow GB et al (2003) Phase I therapy study with (186)Re-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with head and neck squamous cell carcinoma. Clin Cancer Res 9(10 Pt 2):3961S–3972SPubMedGoogle Scholar
  123. 123.
    Colnot DR, Wilhelm AJ, Cloos J, Roos JC, de Bree R, Quak JJ, Snow GB, van Dongen GA (2001) Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy. J Nucl Med 42(9):1364–1367PubMedGoogle Scholar
  124. 124.
    Colnot DR, Ossenkoppele GJ, Roos JC, Quak JJ, de Bree R, Börjesson PK, Huijgens PC, Snow GB, van Dongen GAMS (2002) Reinfusion of unprocessed, granulocyte colony-stimulating factor-stimulated whole blood allows dose escalation of 186Relabeled chimeric monoclonal antibody U36 radioimmunotherapy in a phase I dose escalation study. Clin Cancer Res 8(11):3401–3406PubMedGoogle Scholar
  125. 125.
    Stroomer JW, Roos JC, Sproll M, Quak JJ, Heider KH, Wilhelm BJ, Castelijns JA, Meyer R, Kwakkelstein MO et al (2000) Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients. Clin Cancer Res 6(8):3046–3055PubMedGoogle Scholar
  126. 126.
    Colnot DR, Roos JC, de Bree R, Wilhelm AJ, Kummer JA, Hanft G, Heider K, Stehle G, Snow GB et al (2003) Safety, biodistribution, pharmacokinetics, and immunogenicity of 99mTc-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 52(9):576–582PubMedCrossRefGoogle Scholar
  127. 127.
    Tijink BM, Buter J, de Bree R, Giaccone G, Lang MS, Staab A, Leemans CR, van Dongen GAMS (2006) A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res 12(20 Pt 1):6064–6072PubMedCrossRefGoogle Scholar
  128. 128.
    Koppe M, Schaijk FV, Roos J, Leeuwen PV, Heider K, Kuthan H, Bleichrodt R (2004) Safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with early-stage breast cancer. Cancer Biother Radiopharm 19(6):720–729PubMedCrossRefGoogle Scholar
  129. 129.
    Börjesson PKE, Jauw YWS, de Bree R, Roos JC, Castelijns JA, Leemans CR, van Dongen GAMS, Boellaard R (2009) Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients. J Nucl Med 50(11):1828–1836PubMedCrossRefGoogle Scholar
  130. 130.
    Börjesson PKE, Jauw YWS, Boellaard R, de Bree R, Comans EFI, Roos JC, Castelijns JA, Vosjan MJWD, Kummer JA et al (2006) Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. Clin Cancer Res 12(7 Pt 1):2133–2140PubMedCrossRefGoogle Scholar
  131. 131.
    Coradini D, Zorzet S, Rossin R, Scarlata I, Pellizzaro C, Turrin C, Bello M, Cantoni S, Speranza A et al (2004) Inhibition of hepatocellular carcinomas in vitro and hepatic metastases in vivo in mice by the histone deacetylase inhibitor HA-But. Clin Cancer Res 10(14):4822–4830PubMedCrossRefGoogle Scholar
  132. 132.
    Li S, Howell SB (2010) CD44-targeted microparticles for delivery of cisplatin to peritoneal metastases. Mol Pharm 7(1):280–290PubMedCrossRefGoogle Scholar
  133. 133.
    Peer D, Margalit R (2004) Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models. Int J Cancer 108(5):780–789PubMedCrossRefGoogle Scholar
  134. 134.
    Saravanakumar G, Choi KY, Yoon HY, Kim K, Park JH, Kwon IC, Park K (2010) Hydrotropic hyaluronic acid conjugates: synthesis, characterization, and implications as a carrier of paclitaxel. Int J Pharm 394(1–2):154–161PubMedCrossRefGoogle Scholar
  135. 135.
    Auzenne E, Ghosh SC, Khodadadian M, Rivera B, Farquhar D, Price RE, Ravoori M, Kundra V, Freedman RS et al (2007) Hyaluronic acid-paclitaxel: antitumor efficacy against CD44(+) human ovarian carcinoma xenografts. Neoplasia 9(6):479–486PubMedCrossRefGoogle Scholar
  136. 136.
    Yang K, Tang Y, Habermehl GK, Iczkowski KA (2010) Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity. BMC Cancer 10:16PubMedCrossRefGoogle Scholar
  137. 137.
    Cordo Russo RI, García MG, Alaniz L, Blanco G, Alvarez E, Hajos SE (2008) Hyaluronan oligosaccharides sensitize lymphoma resistant cell lines to vincristine by modulating P-glycoprotein activity and PI3K/Akt pathway. Int J Cancer 122(5):1012–1018PubMedCrossRefGoogle Scholar
  138. 138.
    Nagel S, Hirschmann P, Dirnhofer S, Günthert U, Tzankov A (2010) Coexpression of CD44 variant isoforms and receptor for hyaluronic acid-mediated motility (RHAMM, CD168) is an International Prognostic Index and C-MYC gene status-independent predictor of poor outcome in diffuse large B-cell lymphomas. Exp Hematol 38(1):38–45PubMedCrossRefGoogle Scholar
  139. 139.
    Ohwada C, Nakaseko C, Koizumi M, Takeuchi M, Ozawa S, Naito M, Tanaka H, Oda K, Cho R et al (2008) CD44 and hyaluronan engagement promotes dexamethasone resistance in human myeloma cells. Eur J Haematol 80(3):245–250PubMedCrossRefGoogle Scholar
  140. 140.
    Tajima K, Ohashi R, Sekido Y, Hida T, Nara T, Hashimoto M, Iwakami S, Minakata K, Yae T et al (2010) Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene 29(13):1941–1951PubMedCrossRefGoogle Scholar
  141. 141.
    Runnels HA, Weber GL, Min J, Kudlacz EM, Zobel JF, Donovan CB, Thiede MA, Zhang J, Alpert RB et al (2010) PF-03475952: a potent and neutralizing fully human anti-CD44 antibody for therapeutic applications in inflammatory diseases. Adv Ther 27(3):168–180PubMedCrossRefGoogle Scholar
  142. 142.
    Grosso S, Puissant A, Dufies M, Colosetti P, Jacquel A, Lebrigand K, Barbry P, Deckert M, Cassuto JP et al (2009) Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors. Mol Cancer Ther 8(7):1924–1933PubMedCrossRefGoogle Scholar
  143. 143.
    Bourguignon LYW, Singleton PA, Diedrich F (2004) Hyaluronan-CD44 interaction with Rac1-dependent protein kinase N-gamma promotes phospholipase Cgamma1 activation, Ca(2+) signaling, and cortactin-cytoskeleton function leading to keratinocyte adhesion and differentiation. J Biol Chem 279(28):29654–29669PubMedCrossRefGoogle Scholar
  144. 144.
    Lin YH, Yang-Yen HF (2001) The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. J Biol Chem 276(49):46024–46030PubMedCrossRefGoogle Scholar
  145. 145.
    Hamilton SR, Fard SF, Paiwand FF, Tolg C, Veiseh M, Wang C, McCarthy JB, Bissell MJ, Koropatnick J et al (2007) The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells. J Biol Chem 282(22):16667–16680PubMedCrossRefGoogle Scholar
  146. 146.
    Eshkar Sebban L, Ronen D, Levartovsky D, Elkayam O, Caspi D, Aamar S, Amital H, Rubinow A, Golan I et al (2007) The involvement of CD44 and its novel ligand galectin-8 in apoptotic regulation of autoimmune inflammation. J Immunol 179(2):1225–1235PubMedGoogle Scholar
  147. 147.
    Sherman L, Wainwright D, Ponta H, Herrlich P (1998) A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth. Genes Dev 12(7):1058–1071PubMedCrossRefGoogle Scholar
  148. 148.
    Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H (2002) CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 16(23):3074–3086PubMedCrossRefGoogle Scholar
  149. 149.
    Recio JA, Merlino G (2003) Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1. Cancer Res 63(7):1576–1582PubMedGoogle Scholar
  150. 150.
    Damm S, Koefinger P, Stefan M, Wels C, Mehes G, Richtig E, Kerl H, Otte M, Schaider H (2010) HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta. J Invest Dermatol 130(7):1893–1903PubMedCrossRefGoogle Scholar
  151. 151.
    Bennett KL, Jackson DG, Simon JC, Tanczos E, Peach R, Modrell B, Stamenkovic I, Plowman G, Aruffo A (1995) CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol 128(4):687–698PubMedCrossRefGoogle Scholar
  152. 152.
    Yu W, Woessner JF, McNeish JD, Stamenkovic I (2002) CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 16(3):307–323PubMedCrossRefGoogle Scholar
  153. 153.
    Monaghan M, Mulligan KA, Gillespie H, Trimble A, Winter P, Johnston PG, McCormick D (2000) Epidermal growth factor up-regulates CD44-dependent astrocytoma invasion in vitro. J Pathol 192(4):519–525PubMedCrossRefGoogle Scholar
  154. 154.
    Tremmel M, Matzke A, Albrecht I, Laib AM, Olaku V, Ballmer-Hofer K, Christofori G, Héroult M, Augustin HG et al (2009) A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis. Blood 114(25):5236–5244PubMedCrossRefGoogle Scholar
  155. 155.
    Bourguignon LY, Zhu H, Chu A, Iida N, Zhang L, Hung MC (1997) Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation. J Biol Chem 272(44):27913–27918PubMedCrossRefGoogle Scholar
  156. 156.
    Bourguignon LYW, Peyrollier K, Gilad E, Brightman A (2007) Hyaluronan-CD44 interaction with neural Wiskott–Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells. J Biol Chem 282(2):1265–1280PubMedCrossRefGoogle Scholar
  157. 157.
    Ito T, Williams JD, Fraser D, Phillips AO (2004) Hyaluronan attenuates transforming growth factor-beta1-mediated signaling in renal proximal tubular epithelial cells. Am J Pathol 164(6):1979–1988PubMedCrossRefGoogle Scholar
  158. 158.
    Takahashi K, Eto H, Tanabe KK (1999) Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma cells. Int J Cancer 80(3):387–395PubMedCrossRefGoogle Scholar
  159. 159.
    Thanakit V, Sampatanukul P, Ruangvejvorachai P, Keelawat S (2005) The association of co-expression of CD44v4/MMP-9 with different nodal status in high-grade breast carcinoma patients. J Med Assoc Thai 88(Suppl 4):S30–S35PubMedGoogle Scholar
  160. 160.
    Julovi SM, Ito H, Nishitani K, Jackson CJ, Nakamura T (2010) Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res 2:258–264Google Scholar
  161. 161.
    Denning SM, Le PT, Singer KH, Haynes BF (1990) Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation. J Immunol 144(1):7–15PubMedGoogle Scholar
  162. 162.
    Zhang L, Ma H, Greyner HJ, Zuo W, Mummert ME (2010) Inhibition of cell proliferation by CD44: Akt is inactivated and EGR-1 is down-regulated. Cell Prolif 43(4):385–395PubMedCrossRefGoogle Scholar
  163. 163.
    Gore Y, Starlets D, Maharshak N, Becker-Herman S, Kaneyuki U, Leng L, Bucala R, Shachar I (2008) Macrophage migration inhibitory factor induces B cell survival by activation of a CD74–CD44 receptor complex. J Biol Chem 283(5):2784–2792PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Magdalena Katharina Hertweck
    • 1
  • Felix Erdfelder
    • 1
  • Karl-Anton Kreuzer
    • 1
  1. 1.Department I of Internal MedicineUniversity at CologneCologneGermany

Personalised recommendations