Immunologic Research

, Volume 49, Issue 1–3, pp 160–172 | Cite as

Intracellular osteopontin (iOPN) and immunity

  • Makoto Inoue
  • Mari L. ShinoharaEmail author


Osteopontin (OPN) is a protein involved in various pathophysiological events. OPN has been studied as a secreted protein, but recent reports showed that OPN can be found in the cytoplasm and the nucleus. Therefore, some OPN molecules are not secreted and stay in cells. Such intracellular OPN (iOPN) has biological functions distinct from secreted OPN (sOPN). iOPN is involved in cytoskeletal rearrangement and in signal transduction pathways downstream of innate immune receptors, such as Toll-like receptors (TLRs), as an adaptor or scaffolding protein. Although sOPN and iOPN are generated from the same Opn mRNA species, biological outcomes mediated by two isoforms can be different. It would be necessary to delineate which isoform of OPN is responsible for pathophysiological events.


Osteopontin (OPN) Intracellular OPN (iOPN) Secreted OPN (sOPN) Innate immunity EAE MS Autoimmune diseases T helper cell polarization Dendritic cells (DCs) 



We thank Dr. David Denhardt and Mr. Michael Brown for critical reading of our manuscript.


  1. 1.
    Senger DR, Wirth DF, Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell. 1979;16:885–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Oldberg A, Franzen A, Heinegard D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci USA. 1986;83:8819–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Craig AM, Smith JH, Denhardt DT. Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 1989;264:9682–9.PubMedGoogle Scholar
  4. 4.
    Patarca R, Freeman GJ, Singh RP, Wei FY, Durfee T, Blattner F, et al. Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med. 1989;170:145–61.PubMedCrossRefGoogle Scholar
  5. 5.
    Saitoh Y, Kuratsu J, Takeshima H, Yamamoto S, Ushio Y. Expression of osteopontin in human glioma. Its correlation with the malignancy. Lab Invest. 1995;72:55–63.PubMedGoogle Scholar
  6. 6.
    Denhardt DT, Noda M. Osteopontin expression and function: role in bone remodeling. J Cell Biochem Suppl. 1998;30–31:92–102.PubMedCrossRefGoogle Scholar
  7. 7.
    Gladson CL, Cheresh DA. Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest. 1991;88:1924–32.PubMedCrossRefGoogle Scholar
  8. 8.
    Liaw L, Almeida M, Hart CE, Schwartz SM, Giachelli CM. Osteopontin promotes vascular cell adhesion and spreading and is chemotactic for smooth muscle cells in vitro. Circ Res. 1994;74:214–24.PubMedGoogle Scholar
  9. 9.
    Barry ST, Ludbrook SB, Murrison E, Horgan CM. Analysis of the alpha4beta1 integrin-osteopontin interaction. Exp Cell Res. 2000;258:342–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Barry ST, Ludbrook SB, Murrison E, Horgan CM. A regulated interaction between alpha5beta1 integrin and osteopontin. Biochem Biophys Res Commun. 2000;267:764–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Yokosaki Y, Matsuura N, Sasaki T, Murakami I, Schneider H, Higashiyama S, et al. The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. J Biol Chem. 1999;274:36328–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Diao H, Kon S, Iwabuchi K, Kimura C, Morimoto J, Ito D, et al. Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases. Immunity. 2004;21:539–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Yamamoto N, Sakai F, Kon S, Morimoto J, Kimura C, Yamazaki H, et al. Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J Clin Invest. 2003;112:181–8.PubMedGoogle Scholar
  14. 14.
    Katagiri YU, Sleeman J, Fujii H, Herrlich P, Hotta H, Tanaka K, et al. CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis. Cancer Res. 1999;59:219–26.PubMedGoogle Scholar
  15. 15.
    Schack L, Stapulionis R, Christensen B, Kofod-Olsen E, Skov Sorensen UB, Vorup-Jensen T, et al. Osteopontin enhances phagocytosis through a novel osteopontin receptor, the alphaXbeta2 integrin. J Immunol. 2009;182:6943–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Qin C, Baba O, Butler WT. Post-translational modifications of sibling proteins and their roles in osteogenesis and dentinogenesis. Crit Rev Oral Biol Med. 2004;15:126–36.PubMedCrossRefGoogle Scholar
  17. 17.
    Christensen B, Kazanecki CC, Petersen TE, Rittling SR, Denhardt DT, Sorensen ES. Cell type-specific post-translational modifications of mouse osteopontin are associated with different adhesive properties. J Biol Chem. 2007;282:19463–72.PubMedCrossRefGoogle Scholar
  18. 18.
    Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, et al. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000;287:860–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Weber GF, Zawaideh S, Hikita S, Kumar VA, Cantor H, Ashkar S. Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. J Leukoc Biol. 2002;72:752–61.PubMedGoogle Scholar
  20. 20.
    Kazanecki CC, Kowalski AJ, Ding T, Rittling SR, Denhardt DT. Characterization of anti-osteopontin monoclonal antibodies: binding sensitivity to post-translational modifications. J Cell Biochem. 2007;102:925–35.PubMedCrossRefGoogle Scholar
  21. 21.
    Castellano G, Malaponte G, Mazzarino MC, Figini M, Marchese F, Gangemi P, et al. Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression. Clin Cancer Res. 2008;14:7470–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Chiocchetti A, Indelicato M, Bensi T, Mesturini R, Giordano M, Sametti S, et al. High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation. Blood. 2004;103:1376–82.PubMedCrossRefGoogle Scholar
  23. 23.
    Mochida S, Hashimoto M, Matsui A, Naito M, Inao M, Nagoshi S, et al. Genetic polymorphims in promoter region of osteopontin gene may be a marker reflecting hepatitis activity in chronic hepatitis C patients. Biochem Biophys Res Commun. 2004;313:1079–85.PubMedCrossRefGoogle Scholar
  24. 24.
    D’Alfonso S, Barizzone N, Giordano M, Chiocchetti A, Magnani C, Castelli L, et al. Two single-nucleotide polymorphisms in the 5′ and 3′ ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum. 2005;52:539–47.PubMedCrossRefGoogle Scholar
  25. 25.
    Chiocchetti A, Comi C, Indelicato M, Castelli L, Mesturini R, Bensi T, et al. Osteopontin gene haplotypes correlate with multiple sclerosis development and progression. J Neuroimmunol. 2005;163:172–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Marciano R, D’Annunzio G, Minuto N, Pasquali L, Santamaria A, Di Duca M, et al. Association of alleles at polymorphic sites in the Osteopontin encoding gene in young type 1 diabetic patients. Clin Immunol. 2009;131:84–91.PubMedCrossRefGoogle Scholar
  27. 27.
    de las Fuentes L, Gu CC, Mathews SJ, Reagan JL, Ruthmann NP, Waggoner AD, et al. Osteopontin promoter polymorphism is associated with increased carotid intima-media thickness. J Am Soc Echocardiogr. 2008;21:954–60.CrossRefGoogle Scholar
  28. 28.
    Gao B, Yasui T, Itoh Y, Li Z, Okada A, Tozawa K, et al. Association of osteopontin gene haplotypes with nephrolithiasis. Kidney Int. 2007;72:592–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Schultz J, Lorenz P, Ibrahim SM, Kundt G, Gross G, Kunz M. The functional -443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor. Mol Carcinog. 2009;48:14–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Mirza M, Shaughnessy E, Hurley JK, Vanpatten KA, Pestano GA, He B, et al. Osteopontin-c is a selective marker of breast cancer. Int J Cancer. 2008;122:889–97.PubMedCrossRefGoogle Scholar
  31. 31.
    He B, Mirza M, Weber GF. An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene. 2006;25:2192–202.PubMedCrossRefGoogle Scholar
  32. 32.
    Young MF, Kerr JM, Termine JD, Wewer UM, Wang MG, McBride OW, et al. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN). Genomics. 1990;7:491–502.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev. 2008;19:333–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Buback F, Renkl AC, Schulz G, Weiss JM. Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology. Exp Dermatol. 2009;18:750–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Philip S, Kundu GC. Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha/IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J Biol Chem. 2003;278:14487–97.PubMedCrossRefGoogle Scholar
  36. 36.
    Das R, Philip S, Mahabeleshwar GH, Bulbule A, Kundu GC. Osteopontin: it’s role in regulation of cell motility and nuclear factor kappa B-mediated urokinase type plasminogen activator expression. IUBMB Life. 2005;57:441–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Shinohara ML, Jansson M, Hwang ES, Werneck MB, Glimcher LH, Cantor H. T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc Natl Acad Sci USA. 2005;102:17101–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Murugaiyan G, Mittal A, Weiner HL. Identification of an IL-27/osteopontin axis in dendritic cells and its modulation by IFN-gamma limits IL-17-mediated autoimmune inflammation. Proc Natl Acad Sci USA. 2010;107:11495–500.PubMedCrossRefGoogle Scholar
  39. 39.
    Murugaiyan G, Mittal A, Weiner HL. Increased osteopontin expression in dendritic cells amplifies IL-17 production by CD4+ T cells in experimental autoimmune encephalomyelitis and in multiple sclerosis. J Immunol. 2008;181:7480–8.PubMedGoogle Scholar
  40. 40.
    Shinohara ML, Kim JH, Garcia VA, Cantor H. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity. 2008;29:68–78.PubMedCrossRefGoogle Scholar
  41. 41.
    Ohshima S, Yamaguchi N, Nishioka K, Mima T, Ishii T, Umeshita-Sasai M, et al. Enhanced local production of osteopontin in rheumatoid joints. J Rheumatol. 2002;29:2061–7.PubMedGoogle Scholar
  42. 42.
    Sato T, Nakai T, Tamura N, Okamoto S, Matsuoka K, Sakuraba A, et al. Osteopontin/Eta-1 upregulated in Crohn’s disease regulates the Th1 immune response. Gut. 2005;54:1254–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Matsui A, Mochida S, Ohno A, Nagoshi S, Hirose T, Fujiwara K. Plasma osteopontin levels in patients with fulminant hepatitis. Hepatol Res. 2004;29:202–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Weiss JM, Renkl AC, Maier CS, Kimmig M, Liaw L, Ahrens T, et al. Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes. J Exp Med. 2001;194:1219–29.PubMedCrossRefGoogle Scholar
  45. 45.
    Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 2001;294:1731–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L. Elevated osteopontin levels in active relapsing-remitting multiple sclerosis. Ann Neurol. 2003;53:819–22.PubMedCrossRefGoogle Scholar
  47. 47.
    Yumoto K, Ishijima M, Rittling SR, Tsuji K, Tsuchiya Y, Kon S, et al. Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice. Proc Natl Acad Sci USA. 2002;99:4556–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H. Cutting edge: attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol. 2002;168:2096–9.PubMedGoogle Scholar
  49. 49.
    Shinohara ML, Lu L, Bu J, Werneck MB, Kobayashi KS, Glimcher LH, et al. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol. 2006;7:498–506.PubMedCrossRefGoogle Scholar
  50. 50.
    Hur EM, Youssef S, Haws ME, Zhang SY, Sobel RA, Steinman L. Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat Immunol. 2007;8:74–83.PubMedCrossRefGoogle Scholar
  51. 51.
    Chen M, Chen G, Nie H, Zhang X, Niu X, Zang YC, et al. Regulatory effects of IFN-beta on production of osteopontin and IL-17 by CD4+ T Cells in MS. Eur J Immunol. 2009;39:2525–36.Google Scholar
  52. 52.
    Renkl AC, Wussler J, Ahrens T, Thoma K, Kon S, Uede T, et al. Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype. Blood. 2005;106:946–55.PubMedCrossRefGoogle Scholar
  53. 53.
    Xanthou G, Alissafi T, Semitekolou M, Simoes DC, Economidou E, Gaga M, et al. Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets. Nat Med. 2007;13:570–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Shinohara ML, Cantor H. The bridge between dendritic cells and asthma. Nat Med. 2007;13:536–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Begum MD, Umemura M, Kon S, Yahagi A, Hamada S, Oshiro K, et al. Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin. Microbiol Immunol. 2007;51:135–47.PubMedGoogle Scholar
  56. 56.
    Kurokawa M, Konno S, Takahashi A, Plunkett B, Rittling SR, Matsui Y, et al. Regulatory role of DC-derived osteopontin in systemic allergen sensitization. Eur J Immunol. 2009;39:3323–30.PubMedCrossRefGoogle Scholar
  57. 57.
    Simoes DC, Xanthou G, Petrochilou K, Panoutsakopoulou V, Roussos C, Gratziou C. Osteopontin deficiency protects against airway remodeling and hyperresponsiveness in chronic asthma. Am J Respir Crit Care Med. 2009;179:894–902.PubMedCrossRefGoogle Scholar
  58. 58.
    Wai PY, Guo L, Gao C, Mi Z, Guo H, Kuo PC. Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation. Surgery. 2006;140:132–40.PubMedCrossRefGoogle Scholar
  59. 59.
    Guo H, Wai PY, Mi Z, Gao C, Zhang J, Kuo PC. Osteopontin mediates Stat1 degradation to inhibit iNOS transcription in a cecal ligation and puncture model of sepsis. Surgery. 2008;144:182–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Hwang SM, Lopez CA, Heck DE, Gardner CR, Laskin DL, Laskin JD, et al. Osteopontin inhibits induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial cells. J Biol Chem. 1994;269:711–5.PubMedGoogle Scholar
  61. 61.
    Rittling SR, Matsumoto HN, McKee MD, Nanci A, An XR, Novick KE, et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J Bone Miner Res. 1998;13:1101–11.PubMedCrossRefGoogle Scholar
  62. 62.
    Liaw L, Birk DE, Ballas CB, Whitsitt JS, Davidson JM, Hogan BL. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest. 1998;101:1468–78.PubMedGoogle Scholar
  63. 63.
    Katagiri YU, Murakami M, Mori K, Iizuka J, Hara T, Tanaka K, et al. Non-RGD domains of osteopontin promote cell adhesion without involving alpha v integrins. J Cell Biochem. 1996;62:123–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Sato I, Yamamoto N, Rittling SR, Denhardt DT, Hino M, Morimoro J, et al. Osteopontin is dispensable for protection against high load systemic fungal infection. Int Immunopharmacol. 2008;8:1441–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Iwata D, Kitamura M, Kitaichi N, Saito Y, Kon S, Namba K, et al. Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA. Exp Eye Res. 2010;90:41–48.CrossRefGoogle Scholar
  66. 66.
    Bourassa B, Monaghan S, Rittling SR. Impaired anti-tumor cytotoxicity of macrophages from osteopontin-deficient mice. Cell Immunol. 2004;227:1–11.PubMedCrossRefGoogle Scholar
  67. 67.
    Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch CA, et al. 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. 2004;198:155–67.PubMedCrossRefGoogle Scholar
  68. 68.
    Zohar R, Lee W, Arora P, Cheifetz S, McCulloch C, Sodek J. Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal rat calvarial cells. J Cell Physiol. 1997;170:88–100.PubMedCrossRefGoogle Scholar
  69. 69.
    Zohar R, Suzuki N, Suzuki K, Arora P, Glogauer M, McCulloch CA, et al. Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. J Cell Physiol. 2000;184:118–30.PubMedCrossRefGoogle Scholar
  70. 70.
    Suzuki K, Takeyama S, Sakai Y, Yamada S, Shinoda H. Current topics in pharmacological research on bone metabolism: inhibitory effects of bisphosphonates on the differentiation and activity of osteoclasts. J Pharmacol Sci. 2006;100:189–94.PubMedCrossRefGoogle Scholar
  71. 71.
    Shinohara ML, Kim HJ, Kim JH, Garcia VA, Cantor H. Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc Natl Acad Sci USA. 2008;105:7235–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Junaid A, Moon MC, Harding GE, Zahradka P. Osteopontin localizes to the nucleus of 293 cells and associates with polo-like kinase-1. Am J Physiol Cell Physiol. 2007;292:C919–26.PubMedCrossRefGoogle Scholar
  73. 73.
    Wung JK, Perry G, Kowalski A, Harris PL, Bishop GM, Trivedi MA, et al. Increased expression of the remodeling- and tumorigenic-associated factor osteopontin in pyramidal neurons of the Alzheimer’s disease brain. Curr Alzheimer Res. 2007;4:67–72.PubMedCrossRefGoogle Scholar
  74. 74.
    Baliga SS, Merrill GF, Shinohara ML, Denhardt DT. Osteopontin expression during early cerebral ischemia-reperfusion in rats: enhanced expression in the right cortex is suppressed by acetaminophen. PLoS One. in press.Google Scholar
  75. 75.
    Cantor H, Shinohara ML. Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol. 2009;9:137–41.PubMedCrossRefGoogle Scholar
  76. 76.
    Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N. PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia. Proc Natl Acad Sci USA. 2009;106:15807–12.PubMedCrossRefGoogle Scholar
  77. 77.
    Nystrom T, Duner P, Hultgardh-Nilsson A. A constitutive endogenous osteopontin production is important for macrophage function and differentiation. Exp Cell Res. 2007;313:1149–60.PubMedCrossRefGoogle Scholar
  78. 78.
    Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. Mol Cell Biol. 1991;11:573–7.PubMedGoogle Scholar
  79. 79.
    Arnaud E, Touriol C, Boutonnet C, Gensac MC, Vagner S, Prats H, et al. A new 34-kilodalton isoform of human fibroblast growth factor 2 is cap dependently synthesized by using a non-AUG start codon and behaves as a survival factor. Mol Cell Biol. 1999;19:505–14.PubMedGoogle Scholar
  80. 80.
    Acland P, Dixon M, Peters G, Dickson C. Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon. Nature. 1990;343:662–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Lock P, Ralph S, Stanley E, Boulet I, Ramsay R, Dunn AR. Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization. Mol Cell Biol. 1991;11:4363–70.PubMedGoogle Scholar
  82. 82.
    Huez I, Bornes S, Bresson D, Creancier L, Prats H. New vascular endothelial growth factor isoform generated by internal ribosome entry site-driven CUG translation initiation. Mol Endocrinol. 2001;15:2197–210.PubMedCrossRefGoogle Scholar
  83. 83.
    Takahashi K, Maruyama M, Tokuzawa Y, Murakami M, Oda Y, Yoshikane N, et al. Evolutionarily conserved non-AUG translation initiation in NAT1/p97/DAP5 (EIF4G2). Genomics. 2005;85:360–71.PubMedCrossRefGoogle Scholar
  84. 84.
    Suzuki K, Zhu B, Rittling SR, Denhardt DT, Goldberg HA, McCulloch CA, et al. Colocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts. J Bone Miner Res. 2002;17:1486–97.PubMedCrossRefGoogle Scholar
  85. 85.
    Zohar R, Cheifetz S, McCulloch CA, Sodek J. Analysis of intracellular osteopontin as a marker of osteoblastic cell differentiation and mesenchymal cell migration. Eur J Oral Sci. 1998;106(Suppl 1):401–7.PubMedGoogle Scholar
  86. 86.
    Inoue M, Moriwaki Y, Arikawa T, Chen Y-H, Oh YJ, Oliver T, et al. Cutting Edge: Critical role of intracellular osteopontin in anti-fungal innate immune responses. J Immunol. in press.Google Scholar
  87. 87.
    Heilmann K, Hoffmann U, Witte E, Loddenkemper C, Sina C, Schreiber S, et al. Osteopontin as two-sided mediator of intestinal inflammation. J Cell Mol Med. 2009;13:1162–74.PubMedCrossRefGoogle Scholar
  88. 88.
    Mi Z, Guo H, Russell MB, Liu Y, Sullenger BA, Kuo PC. RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol Ther. 2009;17:153–61.PubMedCrossRefGoogle Scholar
  89. 89.
    Bellahcene A, Castronovo V, Ogbureke KU, Fisher LW, Fedarko NS. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat Rev Cancer. 2008;8:212–26.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Immunology, School of MedicineDuke UniversityDurhamUSA

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