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Intracellular osteopontin (iOPN) and immunity

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Abstract

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.

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References

  1. Senger DR, Wirth DF, Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell. 1979;16:885–93.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  6. Denhardt DT, Noda M. Osteopontin expression and function: role in bone remodeling. J Cell Biochem Suppl. 1998;30–31:92–102.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  9. Barry ST, Ludbrook SB, Murrison E, Horgan CM. Analysis of the alpha4beta1 integrin-osteopontin interaction. Exp Cell Res. 2000;258:342–51.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  31. He B, Mirza M, Weber GF. An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene. 2006;25:2192–202.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  33. Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev. 2008;19:333–45.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  54. Shinohara ML, Cantor H. The bridge between dendritic cells and asthma. Nat Med. 2007;13:536–8.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  66. Bourassa B, Monaghan S, Rittling SR. Impaired anti-tumor cytotoxicity of macrophages from osteopontin-deficient mice. Cell Immunol. 2004;227:1–11.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  75. Cantor H, Shinohara ML. Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol. 2009;9:137–41.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

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

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  1. Department of Immunology, School of Medicine, Duke University, 338 Jones Building, DUMC 3010, Durham, NC, 27710, USA

    Makoto Inoue & Mari L. Shinohara

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Inoue, M., Shinohara, M.L. Intracellular osteopontin (iOPN) and immunity. Immunol Res 49, 160–172 (2011). https://doi.org/10.1007/s12026-010-8179-5

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