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Pre- and post-translational regulation of osteopontin in cancer

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  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

Osteopontin (OPN) is a matricellular protein that binds to a number of cell surface receptors including integrins and CD44. It is expressed in many tissues and secreted into body fluids including blood, milk and urine. OPN plays important physiological roles in bone remodeling, immune response and inflammation. It is also a tumour-associated protein, and elevated OPN levels are associated with tumour formation, progression and metastasis. Research has revealed a promising role for OPN as a cancer biomarker. OPN is subject to alternative splicing, as well as post-translational modifications such as phosphorylation, glycosylation and proteolytic cleavage. Functional differences have been revealed for different isoforms and post-translational modifications. The pattern of isoform expression and post-translational modification is cell-type specific and may influence the potential role of OPN in malignancy and as a cancer biomarker.

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Abbreviations

ECM:

Extracellular matrix

ELISA:

Enzyme-linked immunosorbent assay

HCC:

Hepatocellular carcinoma

HNSCC:

Head and neck squamous cell carcinoma

MM:

Malignant mesothelioma

MMP:

Matrix metalloproteinase

mRNA:

Messenger ribonucleic acid

NSCLC:

Non-small cell lung cancer

OPN:

Osteopontin

PDA:

Pancreatic ductal adenocarcinoma

Q:

Glutamine

qRT-PCR:

Quantitative real time polymerase chain reaction

RT-PCR:

Real time polymerase chain reaction

RGD:

Arginine-Glycine-Aspartic acid

siRNA:

Small interfering ribonucleic acid

shRNA:

Short hairpin ribonucleic acid

SVVYGLR:

Serine-Valine-Valine-Tyrosine-Glycine-Leucine-Arginine

TG2:

Tissue transglutaminase

uPA:

Urokinase plasminogen activator

References

  • Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L (2001) Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 276(30):28261–28267

    Article  PubMed  CAS  Google Scholar 

  • Agrawal D, Chen T, Irby R, Quackenbush J, Chambers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ (2002) Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94(7):513–521

    PubMed  CAS  Google Scholar 

  • Allan AL, George R, Vantyghem SA, Lee MW, Hodgson NC, Engel CJ, Holliday RL, Girvan DP, Scott LA, Postenka CO, Al-Katib W, Stitt LW, Uede T, Chambers AF, Tuck AB (2006) Role of the integrin-binding protein osteopontin in lymphatic metastasis of breast cancer. Am J Pathol 169(1):233–246

    Article  PubMed  CAS  Google Scholar 

  • Al-Shami R, Sorensen ES, Ek-Rylander B, Andersson G, Carson DD, Farach-Carson MC (2005) Phosphorylated osteopontin promotes migration of human choriocarcinoma cells via a p70 S6 kinase-dependent pathway. J Cell Biochem 94(6):1218–1233

    Article  PubMed  CAS  Google Scholar 

  • Anborgh PH, Wilson SM, Tuck AB, Winquist E, Schmidt N, Hart R, Kon S, Maeda M, Uede T, Stitt LW, Chambers AF (2009) New dual monoclonal ELISA for measuring plasma osteopontin as a biomarker associated with survival in prostate cancer: clinical validation and comparison of multiple ELISAs. Clin Chem 55(5):895–903

    Article  PubMed  CAS  Google Scholar 

  • Anborgh PH, Mutrie JC, Tuck AB, Chambers AF (2010) Role of the metastasis-promoting protein osteopontin in the tumor microenvironment. J Cell Mol Med 14(8):2037–2044

    Article  PubMed  CAS  Google Scholar 

  • Bache M, Kappler M, Wichmann H, Rot S, Hahnel A, Greither T, Said HM, Kotzsch M, Wurl P, Taubert H, Vordermark D (2010) Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients. BMC Cancer 10:132

    Article  PubMed  CAS  Google Scholar 

  • Bao LH, Sakaguchi H, Fujimoto J, Tamaya T (2007) Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers. J Biomed Sci 14(3):373–381

    Article  PubMed  CAS  Google Scholar 

  • Blasberg JD, Goparaju CM, Pass HI, Donington JS (2009) Lung cancer osteopontin isoforms exhibit angiogenic functional heterogeneity. J Thorac Cardiovasc Surg 139(6):1587–1593

    Article  PubMed  CAS  Google Scholar 

  • Blasberg JD, Pass HI, Goparaju CM, Flores RM, Lee S, Donington JS (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28(6):936–941

    Article  PubMed  CAS  Google Scholar 

  • Bramwell VH, Tuck AB, Wilson SM, Stitt LW, Cherian AK, Rorke SC, Al-Katib W, Postenka CO, Chambers AF (2005) Expression of osteopontin and HGF/met in adult soft tissue tumors. Cancer Biol Ther 4(12):1336–1341

    Article  PubMed  CAS  Google Scholar 

  • Bramwell VH, Doig GS, Tuck AB, Wilson SM, Tonkin KS, Tomiak A, Perera F, Vandenberg TA, Chambers AF (2006) Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clin Cancer Res 12(11 Pt 1):3337–3343

    Article  PubMed  CAS  Google Scholar 

  • Brinkman BM (2004) Splice variants as cancer biomarkers. Clin Biochem 37(7):584–594

    Article  PubMed  CAS  Google Scholar 

  • Brown LF, Papadopoulos-Sergiou A, Berse B, Manseau EJ, Tognazzi K, Perruzzi CA, Dvorak HF, Senger DR (1994) Osteopontin expression and distribution in human carcinomas. Am J Pathol 145(3):610–623

    PubMed  CAS  Google Scholar 

  • Cao Z, Dai J, Fan K, Wang H, Ji G, Li B, Zhang D, Hou S, Qian W, Zhao J, Wang H, Guo Y (2008) A novel functional motif of osteopontin for human lymphocyte migration and survival. Mol Immunol 45(14):3683–3692

    Article  PubMed  CAS  Google Scholar 

  • Cazet A, Julien S, Bobowski M, Burchell J, Delannoy P (2010) Tumour-associated carbohydrate antigens in breast cancer. Breast Cancer Res 12(3):204

    Article  PubMed  CAS  Google Scholar 

  • Chae S, Jun HO, Lee EG, Yang SJ, Lee DC, Jung JK, Park KC, Yeom YI, Kim KW (2009) Osteopontin splice variants differentially modulate the migratory activity of hepatocellular carcinoma cell lines. Int J Oncol 35(6):1409–1416

    PubMed  CAS  Google Scholar 

  • Chakraborty G, Jain S, Patil TV, Kundu GC (2008) Down-regulation of osteopontin attenuates breast tumour progression in vivo. J Cell Mol Med 12(6A):2305–2318

    Article  PubMed  CAS  Google Scholar 

  • Chambers AF, Wilson SM, Kerkvliet N, O’Malley FP, Harris JF, Casson AG (1996) Osteopontin expression in lung cancer. Lung Cancer 15(3):311–323

    Article  PubMed  CAS  Google Scholar 

  • Chang PL, Harkins L, Hsieh YH, Hicks P, Sappayatosok K, Yodsanga S, Swasdison S, Chambers AF, Elmets CA, Ho KJ (2008) Osteopontin expression in normal skin and non-melanoma skin tumors. J Histochem Cytochem 56(1):57–66

    Article  PubMed  CAS  Google Scholar 

  • Chen RX, Xia YH, Xue TC, Zhang H, Ye SL (2011) Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncol Rep 25(3):803-808

    Google Scholar 

  • Chien CY, Su CY, Chuang HC, Fang FM, Huang HY, Chen CH, Chen CM, Huang CC (2009) Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma. Oral Oncol 45(9):798–802

    Article  PubMed  CAS  Google Scholar 

  • Cho HJ, Cho HJ, Kim HS (2009) Osteopontin: A multifunctional protein at the crossroads of inflammation, atherosclerosis, and vascular calcification. Curr Atheroscler Rep 11(3):206–213

    Article  PubMed  CAS  Google Scholar 

  • Christensen B, Nielsen MS, Haselmann KF, Petersen TE, Sorensen ES (2005) Post-translationally modified residues of native human osteopontin are located in clusters: Identification of 36 phosphorylation and five O-glycosylation sites and their biological implications. Biochem J 390(Pt 1):285–292

    PubMed  CAS  Google Scholar 

  • Christensen B, Kazanecki CC, Petersen TE, Rittling SR, Denhardt DT, Sorensen ES (2007) Cell type-specific post-translational modifications of mouse osteopontin are associated with different adhesive properties. J Biol Chem 282(27):19463–19472

    Article  PubMed  CAS  Google Scholar 

  • Christensen B, Petersen TE, Sorensen ES (2008) Post-translational modification and proteolytic processing of urinary osteopontin. Biochem J 411(1):53–61

    Article  PubMed  CAS  Google Scholar 

  • Collighan RJ, Griffin M (2009) Transglutaminase 2 cross-linking of matrix proteins: Biological significance and medical applications. Amino Acids 36(4):659–670

    Article  PubMed  CAS  Google Scholar 

  • Cook AC, Tuck AB, McCarthy S, Turner JG, Irby RB, Bloom GC, Yeatman TJ, Chambers AF (2005) Osteopontin induces multiple changes in gene expression that reflect the six “hallmarks of cancer” in a model of breast cancer progression. Mol Carcinog 43(4):225–236

    Article  PubMed  CAS  Google Scholar 

  • Coppola D, Szabo M, Boulware D, Muraca P, Alsarraj M, Chambers AF, Yeatman TJ (2004) Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res 10(1 Pt 1):184–190

    Article  PubMed  CAS  Google Scholar 

  • Courter D, Cao H, Kwok S, Kong C, Banh A, Kuo P, Bouley DM, Vice C, Brustugun OT, Denko NC, Koong AC, Giaccia A, Le QT (2010) The RGD domain of human osteopontin promotes tumor growth and metastasis through activation of survival pathways. PLoS One 5(3):e9633

    Article  PubMed  CAS  Google Scholar 

  • Cui R, Takahashi F, Ohashi R, Gu T, Yoshioka M, Nishio K, Ohe Y, Tominaga S, Takagi Y, Sasaki S, Fukuchi Y, Takahashi K (2007) Abrogation of the interaction between osteopontin and alphavbeta3 integrin reduces tumor growth of human lung cancer cells in mice. Lung Cancer 57(3):302–310

    Article  PubMed  Google Scholar 

  • Dai J, Cao Z, Kang Y, Fan K, Ji G, Yang H, Wang H, Gao J, Wang H, Guo Y (2009) A functional motif QLYxxYP is essential for osteopontin induced T lymphocyte activation and migration. Biochem Biophys Res Commun 380(3):715–720

    Article  PubMed  CAS  Google Scholar 

  • Dai J, Li B, Shi J, Peng L, Zhang D, Qian W, Hou S, Zhao L, Gao J, Cao Z, Zhao J, Wang H, Guo Y (2010) A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol Immunother 59(3):355–366

    Article  PubMed  CAS  Google Scholar 

  • Dean RA, Overall CM (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome. Mol Cell Proteomics 6(4):611–623

    Article  PubMed  CAS  Google Scholar 

  • Ecarot-Charrier B, Bouchard F, Delloye C (1989) Bone sialoprotein II synthesized by cultured osteoblasts contains tyrosine sulfate. J Biol Chem 264(33):20049–20053

    PubMed  CAS  Google Scholar 

  • Ek-Rylander B, Andersson G (2010) Osteoclast migration on phosphorylated osteopontin is regulated by endogenous tartrate-resistant acid phosphatase. Exp Cell Res 316(3):443–451

    Article  PubMed  CAS  Google Scholar 

  • Ek-Rylander B, Flores M, Wendel M, Heinegard D, Andersson G (1994) Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate-resistant acid phosphatase. modulation of osteoclast adhesion in vitro. J Biol Chem 269(21):14853–14856

    PubMed  CAS  Google Scholar 

  • Forootan SS, Foster CS, Aachi VR, Adamson J, Smith PH, Lin K, Ke Y (2006) Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 118(9):2255–2261

    Article  PubMed  CAS  Google Scholar 

  • Furger KA, Menon RK, Tuck AB, Bramwell VH, Chambers AF (2001) The functional and clinical roles of osteopontin in cancer and metastasis. Curr Mol Med 1(5):621–632

    Article  PubMed  CAS  Google Scholar 

  • Gaumann A, Petrow P, Mentzel T, Mayer E, Dahm M, Otto M, Kirkpatrick CJ, Kriegsmann J (2001) Osteopontin expression in primary sarcomas of the pulmonary artery. Virchows Arch 439(5):668–674

    PubMed  CAS  Google Scholar 

  • Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19(7):615–622

    Article  PubMed  CAS  Google Scholar 

  • Goparaju CM, Pass HI, Blasberg JD, Hirsch N, Donington JS (2010) Functional heterogeneity of osteopontin isoforms in non-small cell lung cancer. J Thorac Oncol 5(10):1516–1523

    Article  PubMed  Google Scholar 

  • Grassinger J, Haylock DN, Storan MJ, Haines GO, Williams B, Whitty GA, Vinson AR, Be CL, Li S, Sorensen ES, Tam PP, Denhardt DT, Sheppard D, Choong PF, Nilsson SK (2009) Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood 114(1):49–59

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  PubMed  CAS  Google Scholar 

  • He B, Mirza M, Weber GF (2006) An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene 25(15):2192–2202

    Article  PubMed  CAS  Google Scholar 

  • Higashikawa F, Eboshida A, Yokosaki Y (2007) Enhanced biological activity of polymeric osteopontin. FEBS Lett 581(14):2697–2701

    Article  PubMed  CAS  Google Scholar 

  • Hijiya N, Setoguchi M, Matsuura K, Higuchi Y, Akizuki S, Yamamoto S (1994) Cloning and characterization of the human osteopontin gene and its promoter. Biochem J 303(Pt 1):255–262

    PubMed  CAS  Google Scholar 

  • Hotte SJ, Winquist EW, Stitt L, Wilson SM, Chambers AF (2002) Plasma osteopontin: associations with survival and metastasis to bone in men with hormone-refractory prostate carcinoma. Cancer 95(3):506–512

    Article  PubMed  CAS  Google Scholar 

  • Imano M, Satou T, Itoh T, Sakai K, Ishimaru E, Yasuda A, Peng YF, Shinkai M, Akai F, Yasuda T, Imamoto H, Okuno K, Ito H, Shiozaki H, Ohyanagi H (2009) Immunohistochemical expression of osteopontin in gastric cancer. J Gastrointest Surg 13(9):1577–1582

    Article  PubMed  Google Scholar 

  • Irby RB, McCarthy SM, Yeatman TJ (2004) Osteopontin regulates multiple functions contributing to human colon cancer development and progression. Clin Exp Metastasis 21(6):515–523

    Article  PubMed  CAS  Google Scholar 

  • Ivanov SV, Ivanova AV, Goparaju CM, Chen Y, Beck A, Pass HI (2009) Tumorigenic properties of alternative osteopontin isoforms in mesothelioma. Biochem Biophys Res Commun 382(3):514–518

    Article  PubMed  CAS  Google Scholar 

  • Julien S, Picco G, Sewell R, Vercoutter-Edouart AS, Tarp M, Miles D, Clausen H, Taylor-Papadimitriou J, Burchell JM (2009) Sialyl-tn vaccine induces antibody-mediated tumour protection in a relevant murine model. Br J Cancer 100(11):1746–1754

    Article  PubMed  CAS  Google Scholar 

  • Kaartinen MT, El-Maadawy S, Rasanen NH, McKee MD (2002) Tissue transglutaminase and its substrates in bone. J Bone Miner Res 17(12):2161–2173

    Article  PubMed  CAS  Google Scholar 

  • Kaartinen MT, Murshed M, Karsenty G, McKee MD (2007) Osteopontin upregulation and polymerization by transglutaminase 2 in calcified arteries of matrix gla protein-deficient mice. J Histochem Cytochem 55(4):375–386

    Article  PubMed  CAS  Google Scholar 

  • Kazanecki CC, Uzwiak DJ, Denhardt DT (2007) Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J Cell Biochem 102(4):912–924

    Article  PubMed  CAS  Google Scholar 

  • Keykhosravani M, Doherty-Kirby A, Zhang C, Brewer D, Goldberg HA, Hunter GK, Lajoie G (2005) Comprehensive identification of post-translational modifications of rat bone osteopontin by mass spectrometry. Biochemistry 44(18):6990–7003

    Article  PubMed  CAS  Google Scholar 

  • Kiefer MC, Bauer DM, Barr PJ (1989) The cDNA and derived amino acid sequence for human osteopontin. Nucleic Acids Res 17(8):3306

    Article  PubMed  CAS  Google Scholar 

  • Kunii Y, Niwa S, Hagiwara Y, Maeda M, Seitoh T, Suzuki T (2009) The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems. Med Mol Morphol 42(3):155–161

    Article  PubMed  CAS  Google Scholar 

  • Kyriakides TR, Bornstein P (2003) Matricellular proteins as modulators of wound healing and the foreign body response. Thromb Haemost 90(6):986–992

    PubMed  CAS  Google Scholar 

  • Lasa M, Chang PL, Prince CW, Pinna LA (1997) Phosphorylation of osteopontin by golgi apparatus casein kinase. Biochem Biophys Res Commun 240(3):602–605

    Article  PubMed  CAS  Google Scholar 

  • Likui W, Hong W, Shuwen Z (2010) Clinical significance of the upregulated osteopontin mRNA expression in human colorectal cancer. J Gastrointest Surg 14(1):74–81

    Article  PubMed  Google Scholar 

  • Lin F, Li Y, Cao J, Fan S, Wen J, Zhu G, Du H, Liang Y (2010) Overexpression of osteopontin in hepatocellular carcinoma and its relationships with metastasis, invasion of tumor cells. Mol Biol Rep

  • Liu H, Chen A, Guo F, Yuan L (2010) A short-hairpin RNA targeting osteopontin downregulates MMP-2 and MMP-9 expressions in prostate cancer PC-3 cells. Cancer Lett 295(1):27–37

    Article  PubMed  CAS  Google Scholar 

  • Mangala LS, Fok JY, Zorrilla-Calancha IR, Verma A, Mehta K (2007) Tissue transglutaminase expression promotes cell attachment, invasion and survival in breast cancer cells. Oncogene 26(17):2459–2470

    Article  PubMed  CAS  Google Scholar 

  • Masuda K, Takahashi N, Tsukamoto Y, Honma H, Kohri K (2000) N-glycan structures of an osteopontin from human bone. Biochem Biophys Res Commun 268(3):814–817

    Article  PubMed  CAS  Google Scholar 

  • Mehta K, Fok J, Miller FR, Koul D, Sahin AA (2004) Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer. Clin Cancer Res 10(23):8068–8076

    Article  PubMed  CAS  Google Scholar 

  • Mi Z, Oliver T, Guo H, Gao C, Kuo PC (2007) Thrombin-cleaved COOH(−) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells. Cancer Res 67(9):4088–4097

    Article  PubMed  CAS  Google Scholar 

  • Mi Z, Guo H, Russell MB, Liu Y, Sullenger BA, Kuo PC (2009) RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol Ther 17(1):153–161

    Article  PubMed  CAS  Google Scholar 

  • Mirza M, Shaughnessy E, Hurley JK, Vanpatten KA, Pestano GA, He B, Weber GF (2008) Osteopontin-c is a selective marker of breast cancer. Int J Cancer 122(4):889–897

    Article  PubMed  CAS  Google Scholar 

  • Nagata T, Todescan R, Goldberg HA, Zhang Q, Sodek J (1989) Sulphation of secreted phosphoprotein I (SPPI, osteopontin) is associated with mineralized tissue formation. Biochem Biophys Res Commun 165(1):234–240

    Article  PubMed  CAS  Google Scholar 

  • Pass HI, Lott D, Lonardo F, Harbut M, Liu Z, Tang N, Carbone M, Webb C, Wali A (2005) Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med 353(15):1564–1573

    Article  PubMed  CAS  Google Scholar 

  • Patani N, Jouhra F, Jiang W, Mokbel K (2008) Osteopontin expression profiles predict pathological and clinical outcome in breast cancer. Anticancer Res 28(6B):4105–4110

    PubMed  CAS  Google Scholar 

  • Prince CW, Dickie D, Krumdieck CL (1991) Osteopontin, a substrate for transglutaminase and factor XIII activity. Biochem Biophys Res Commun 177(3):1205–1210

    Article  PubMed  CAS  Google Scholar 

  • Rangaswami H, Bulbule A, Kundu GC (2004) Nuclear factor-inducing kinase plays a crucial role in osteopontin-induced MAPK/IkappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation. J Biol Chem 279(37):38921–38935

    Article  PubMed  CAS  Google Scholar 

  • Rangaswami H, Bulbule A, Kundu GC (2006) Osteopontin: role in cell signaling and cancer progression. Trends Cell Biol 16(2):79–87

    Article  PubMed  CAS  Google Scholar 

  • Reinholt FP, Hultenby K, Oldberg A, Heinegard D (1990) Osteopontin–a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A 87(12):4473–4475

    Article  PubMed  CAS  Google Scholar 

  • Rittling SR, Chambers AF (2004) Role of osteopontin in tumour progression. Br J Cancer 90(10):1877–1881

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mansson H (2007) The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol Biomarkers Prev 16(6):1087–1097

    Article  PubMed  CAS  Google Scholar 

  • Rudland PS, Platt-Higgins A, El-Tanani M, De Silva RS, Barraclough R, Winstanley JH, Howitt R, West CR (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62(12):3417–3427

    PubMed  CAS  Google Scholar 

  • Saeki Y, Mima T, Ishii T, Ogata A, Kobayashi H, Ohshima S, Ishida T, Tabunoki Y, Kitayama H, Mizuki M, Katada Y, Asaoku H, Kitano M, Nishimoto N, Yoshizaki K, Maeda M, Kon S, Kinoshita N, Uede T, Kawase I (2003) Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications. Br J Haematol 123(2):263–270

    Article  PubMed  CAS  Google Scholar 

  • Saitoh Y, Kuratsu J, Takeshima H, Yamamoto S, Ushio Y (1995) Expression of osteopontin in human glioma. its correlation with the malignancy. Lab Invest 72(1):55–63

    PubMed  CAS  Google Scholar 

  • Salih E, Ashkar S, Gerstenfeld LC, Glimcher MJ (1997) Identification of the phosphorylated sites of metabolically 32P-labeled osteopontin from cultured chicken osteoblasts. J Biol Chem 272(21):13966–13973

    Article  PubMed  CAS  Google Scholar 

  • Schulze EB, Hedley BD, Goodale D, Postenka CO, Al-Katib W, Tuck AB, Chambers AF, Allan AL (2008) The thrombin inhibitor argatroban reduces breast cancer malignancy and metastasis via osteopontin-dependent and osteopontin-independent mechanisms. Breast Cancer Res Treat 112(2):243–254

    Article  PubMed  CAS  Google Scholar 

  • Senger DR, Perruzzi CA, Papadopoulos A (1989) Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation. Anticancer Res 9(5):1291–1299

    PubMed  CAS  Google Scholar 

  • Senger DR, Perruzzi CA, Papadopoulos-Sergiou A, Van de Water L (1994) Adhesive properties of osteopontin: regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol Biol Cell 5(5):565–574

    PubMed  CAS  Google Scholar 

  • Shanmugam V, Chackalaparampil I, Kundu GC, Mukherjee AB, Mukherjee BB (1997) Altered sialylation of osteopontin prevents its receptor-mediated binding on the surface of oncogenically transformed tsB77 cells. Biochemistry 36(19):5729–5738

    Article  PubMed  CAS  Google Scholar 

  • Shevde LA, Samant RS, Paik JC, Metge BJ, Chambers AF, Casey G, Frost AR, Welch DR (2006) Osteopontin knockdown suppresses tumorigenicity of human metastatic breast carcinoma, MDA-MB-435. Clin Exp Metastasis 23(2):123–133

    Article  PubMed  CAS  Google Scholar 

  • Singhal H, Bautista DS, Tonkin KS, O’Malley FP, Tuck AB, Chambers AF, Harris JF (1997) Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res 3(4):605–611

    PubMed  CAS  Google Scholar 

  • Smith LL, Cheung HK, Ling LE, Chen J, Sheppard D, Pytela R, Giachelli CM (1996) Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin. J Biol Chem 271(45):28485–28491

    Article  PubMed  CAS  Google Scholar 

  • Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11(3):279–303

    Article  PubMed  CAS  Google Scholar 

  • Sorensen ES, Rasmussen LK, Moller L, Jensen PH, Hojrup P, Petersen TE (1994) Localization of transglutaminase-reactive glutamine residues in bovine osteopontin. Biochem J 304(Pt 1):13–16

    PubMed  CAS  Google Scholar 

  • Sorensen ES, Hojrup P, Petersen TE (1995) Posttranslational modifications of bovine osteopontin: identification of twenty-eight phosphorylation and three O-glycosylation sites. Protein Sci 4(10):2040–2049

    Article  PubMed  CAS  Google Scholar 

  • Sreekanthreddy P, Srinivasan H, Kumar DM, Nijaguna MB, Sridevi S, Vrinda M, Arivazhagan A, Balasubramaniam A, Hegde AS, Chandramouli BA, Santosh V, Rao MR, Kondaiah P, Somasundaram K (2010) Identification of potential serum biomarkers of glioblastoma: Serum osteopontin levels correlate with poor prognosis. Cancer Epidemiol Biomarkers Prev 19(6):1409–1422

    Article  PubMed  CAS  Google Scholar 

  • Stone MJ, Chuang S, Hou X, Shoham M, Zhu JZ (2009). Tyrosine sulfation: an increasingly recognised post-translational modification of secreted proteins. New Biotechnol 25(5):299–317.

    Article  CAS  Google Scholar 

  • Sullivan J, Blair L, Alnajar A, Aziz T, Ng CY, Chipitsyna G, Gong Q, Witkiewicz A, Weber GF, Denhardt DT, Yeo CJ, Arafat HA (2009) Expression of a prometastatic splice variant of osteopontin, OPNC, in human pancreatic ductal adenocarcinoma. Surgery 146(2):232–240

    Article  PubMed  Google Scholar 

  • Sulzbacher I, Birner P, Trieb K, Lang S, Chott A (2002) Expression of osteopontin and vascular endothelial growth factor in benign and malignant bone tumors. Virchows Arch 441(4):345–349

    Article  PubMed  CAS  Google Scholar 

  • Takafuji V, Forgues M, Unsworth E, Goldsmith P, Wang XW (2007) An osteopontin fragment is essential for tumor cell invasion in hepatocellular carcinoma. Oncogene 26(44):6361–6371

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Takahashi F, Tanabe KK, Takahashi H, Fukuchi Y (1998) The carboxyl-terminal fragment of osteopontin suppresses arginine-glycine-asparatic acid-dependent cell adhesion. Biochem Mol Biol Int 46(6):1081–1092

    PubMed  CAS  Google Scholar 

  • Terpos E, Kiagia M, Karapanagiotou EM, Charpidou A, Dilana KD, Nasothimiou E, Harrington KJ, Polyzos A, Syrigos KN (2009) The clinical significance of serum markers of bone turnover in NSCLC patients: surveillance, management and prognostic implications. Anticancer Res 29(5):1651–1657

    PubMed  CAS  Google Scholar 

  • Tuck AB, Chambers AF (2001) The role of osteopontin in breast cancer: clinical and experimental studies. J Mammary Gland Biol Neoplasia 6(4):419–429

    Article  PubMed  CAS  Google Scholar 

  • Tuck AB, O'Malley FP, Singhal H, Tonkin KS, Harris JF, Bautista D, Chambers AF (1997) Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch Pathol Lab Med 121(6):578–584

    PubMed  CAS  Google Scholar 

  • Tuck AB, O'Malley FP, Singhal H, Harris JF, Tonkin KS, Kerkvliet N, Saad Z, Doig GS, Chambers AF (1998) Osteopontin expression in a group of lymph node negative breast cancer patients. Int J Cancer 79(5):502–508

    Article  PubMed  CAS  Google Scholar 

  • Tuck AB, Arsenault DM, O’Malley FP, Hota C, Ling MC, Wilson SM, Chambers AF (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18(29):4237–4246

    Article  PubMed  CAS  Google Scholar 

  • Tuck AB, Elliott BE, Hota C, Tremblay E, Chambers AF (2000) Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (met). J Cell Biochem 78(3):465–475

    Article  PubMed  CAS  Google Scholar 

  • Tuck AB, Hota C, Wilson SM, Chambers AF (2003) Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways. Oncogene 22(8):1198–1205

    Article  PubMed  CAS  Google Scholar 

  • Tuck AB, Chambers AF, Allan AL (2007) Osteopontin overexpression in breast cancer: knowledge gained and possible implications for clinical management. J Cell Biochem 102(4):859–868

    Article  PubMed  CAS  Google Scholar 

  • Venables JP, Koh CS, Froehlich U, Lapointe E, Couture S, Inkel L, Bramard A, Paquet ER, Watier V, Durand M, Lucier JF, Gervais-Bird J, Tremblay K, Prinos P, Klinck R, Elela SA, Chabot B (2008) Multiple and specific mRNA processing targets for the major human hnRNP proteins. Mol Cell Biol 28(19):6033–6043

    Article  PubMed  CAS  Google Scholar 

  • Wai PY, Kuo PC (2004) The role of osteopontin in tumor metastasis. J Surg Res 121(2):228–241

    Article  PubMed  CAS  Google Scholar 

  • Wai PY, Kuo PC (2008) Osteopontin: Regulation in tumor metastasis. Cancer Metastasis Rev 27(1):103–118

    Article  PubMed  CAS  Google Scholar 

  • Weber GF (2001) The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim Biophys Acta 1552(2):61–85

    PubMed  CAS  Google Scholar 

  • Weber GF, Lett GS, Haubein NC (2010) Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer 103(6):861–869

    Article  PubMed  CAS  Google Scholar 

  • Xuan JW, Hota C, Chambers AF (1994) Recombinant GST-human osteopontin fusion protein is functional in RGD-dependent cell adhesion. J Cell Biochem 54(2):247–255

    Article  PubMed  CAS  Google Scholar 

  • Yan W, Qian C, Zhao P, Zhang J, Shi L, Qian J, Liu N, Fu Z, Kang C, Pu P, You Y (2010) Expression pattern of osteopontin splice variants and its functions on cell apoptosis and invasion in glioma cells. Neuro Oncol 12(8):765–775

    Article  PubMed  CAS  Google Scholar 

  • Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen Y, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9(4):416–423

    Article  PubMed  CAS  Google Scholar 

  • Yokosaki Y, Matsuura N, Sasaki T, Murakami I, Schneider H, Higashiyama S, Saitoh Y, Yamakido M, Taooka Y, Sheppard D (1999) 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 274(51):36328–36334

    Article  PubMed  CAS  Google Scholar 

  • Young MF, Kerr JM, Termine JD, Wewer UM, Wang MG, McBride OW, Fisher LW (1990) cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN). Genomics 7(4):491–502

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Takahashi K, Takahashi F, Shimizu K, Ohshita F, Kameda Y, Maeda K, Nishio K, Fukuchi Y (2001) Differential osteopontin expression in lung cancer. Cancer Lett 171(2):215–222

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Hunter GK, Goldberg HA, Lajoie GA, Yeung KK (2007) An integrated procedure of selective injection, sample stacking and fractionation of phosphopeptides for MALDI MS analysis. Anal Chim Acta 581(2):268–280

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Tsukamoto T, Mizoshita T, Ban H, Suzuki H, Toyoda T, Tatematsu M (2009) Expression of osteopontin and CDX2: indications of phenotypes and prognosis in advanced gastric cancer. Oncol Rep 21(3):609–613

    PubMed  CAS  Google Scholar 

  • Zhao B, Sun T, Meng F, Qu A, Li C, Shen H, Jin Y, Li W (2011) Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer. J Cancer Res Clin Oncol

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Acknowledgements

This work is supported by an award from the Lloyd Carr-Harris Foundation. JCM is supported by a Canadian Graduate Award from the Canadian Institutes of Health Research and a Studentship from the Translational Breast Cancer Research Unit at the London Regional Cancer Program. AFC is a Canada Research Chair in Oncology, supported by the Canada Research Chairs Program.

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Authors and Affiliations

  1. London Regional Cancer Program, 790 Commissioners Road East, London, ON, N6A 4L6, Canada

    Pieter H. Anborgh, Jennifer C. Mutrie, Alan B. Tuck & Ann F. Chambers

  2. Department of Pathology, University of Western Ontario, London, ON, Canada

    Jennifer C. Mutrie, Alan B. Tuck & Ann F. Chambers

  3. London Health Sciences Centre, London, ON, Canada

    Alan B. Tuck

  4. Department of Oncology, University of Western Ontario, London, ON, Canada

    Alan B. Tuck & Ann F. Chambers

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  1. Pieter H. Anborgh
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  2. Jennifer C. Mutrie
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  3. Alan B. Tuck
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  4. Ann F. Chambers
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Correspondence to Ann F. Chambers.

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Anborgh, P.H., Mutrie, J.C., Tuck, A.B. et al. Pre- and post-translational regulation of osteopontin in cancer. J. Cell Commun. Signal. 5, 111–122 (2011). https://doi.org/10.1007/s12079-011-0130-6

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  • DOI: https://doi.org/10.1007/s12079-011-0130-6

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