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Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers

  • Published:
Journal of Biomedical Science

Summary

Osteopontin (OPN) is expressed in various human cancers and associated with tumor progression, invasion and metastasis in many manners. The purpose of this study is to investigate the clinical significance of OPN expression in metastatic lesions of ovarian cancers, since the prognosis of the patients with peritoneal dissemination is extremely poor. In primary tumors and peritoneal metastatic lesions from 40 patients with stage III ovarian cancers, the protein levels of OPN and histoscores were determined by enzyme immunoassay and immunohistochemistry, respectively. Immunohistochemical staining revealed OPN was distributed in the cytoplasm and nuclear compartments of the cancer and stromal cells within and around the tumor. The OPN level was significantly (< 0.05) increased in 32 of 40 metastatic lesions of ovarian cancers. The OPN increased cases identified by immunohistochemical staining were consistent with those identified by the sandwich immunoassay. The prognosis of the 32 patients with significant increase of OPN in ovarian cancers was extremely poor, whereas the 36-month survival rate of the 8 patients with no increase of OPN was 75%. Multivariate analysis revealed that the levels of OPN were independent predictors of prognosis from clinical characteristics (age, lesion size, histological types). OPN might be associated with peritoneal metastasis and its advancement, and that the OPN level in metastatic lesion may be a prognostic indicator in ovarian cancers.

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References

  1. Senger D.R., Wirth D.F., Hynes R.O., (1979) Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell 16: 885–893

    Article  PubMed  CAS  Google Scholar 

  2. Craig A.M., Denhardt D.T., (1991) The murine gene encoding secreted phosphoprotein 1 (osteopontin): promoter structure, activity, and induction in vivo by estrogen and progesterone. Gene 100: 163–171

    Article  PubMed  CAS  Google Scholar 

  3. Denhardt D.T., Guo X., (1993) Osteopontin: a protein with diverse functions. Faseb. J. 7: 1475–1482

    PubMed  CAS  Google Scholar 

  4. Denhardt D.T., Noda M., (1998) Osteopontin expression and function: role in bone remodeling. J. Cell. Biochem. Suppl. 30–31: 92–102

    Article  PubMed  Google Scholar 

  5. O’Regan A., Berman J.S., (2000) Osteopontin: a key cytokine in cell-mediated and granulomatous inflammation. Int. J. Exp. Pathol. 81: 373–390

    Article  PubMed  CAS  Google Scholar 

  6. Weber G.F., (2001) The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim. Biophys. Acta. 1552: 61–85

    PubMed  CAS  Google Scholar 

  7. 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: 255–262

    PubMed  CAS  Google Scholar 

  8. Tuck A.B., O’Malley F.P., Singhal H., Tonkin K.S., Harris J.F., Bautista D., Chambers A.F., (1997) Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch. Pathol. Lab. Med. 121: 578–584

    PubMed  CAS  Google Scholar 

  9. Tuck A.B., O’Malley F.P., Singhal H., Harris J.F., Tonkin K.S., Kerkvliet N., Saad Z., Doig G.S., Chambers A.F., (1998) Osteopontin expression in a group of lymph node negative breast cancer patients. Int. J. Cancer 79: 502–508

    Article  PubMed  CAS  Google Scholar 

  10. Tuck A.B., Arsenault D.M., O’Malley F.P., Hota C., Ling M.C., Wilson S.M., Chambers A.F., (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18: 4237–4246

    Article  PubMed  CAS  Google Scholar 

  11. Rudland P.S., Platt-Higgins A., El-Tanani M., De Silva Rudland S., Barraclough R., Winstanley J.H., Howitt R., West C.R., (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 62: 3417–3427

    PubMed  CAS  Google Scholar 

  12. Shijubo N., Uede T., Kon S., Maeda M., Segawa T., Imada A., Hirasawa M., Abe S., (1999) Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma. Am. J. Respir. Crit. Care Med. 160: 1269–1273

    PubMed  CAS  Google Scholar 

  13. Chambers A.F., Wilson S.M., Kerkvliet N., O’Malley F.P., Harris J.F., Casson A.G., (1996) Osteopontin expression in lung cancer. Lung Cancer 15: 311–323

    Article  PubMed  CAS  Google Scholar 

  14. Schneider S., Yochim J., Brabender J., Uchida K., Danenberg K.D., Metzger R., Schneider P.M., Salonga D., Holscher A.H., Danenberg P.V., (2004) Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin. Cancer Res. 10: 1588–1596

    Article  PubMed  CAS  Google Scholar 

  15. Thalmann G.N., Sikes R.A., Devoll R.E., Kiefer J.A., Markwalder R., Klima I., Farach-Carson C.M., Studer U.E., Chung L.W., (1999) Osteopontin: possible role in prostate cancer progression. Clin. Cancer Res. 5: 2271–2277

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Kim J.H., Skates S.J., Uede T., Wong K.K., Schorge J.O., Feltmate C.M., Berkowitz R.S., Cramer D.W., Mok S.C., (2002) Osteopontin as a potential diagnostic biomarker for ovarian cancer. Jama 287: 1671–1679

    Article  PubMed  CAS  Google Scholar 

  18. Rosen D.G., Wang L., Atkinson J.N., Yu Y., Lu K.H., Diamandis E.P., Hellstrom I., Mok S.C., Liu J., Bast Jr. R.C., (2005) Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol. Oncol. 99: 267–277

    Article  PubMed  CAS  Google Scholar 

  19. Nakae M., Iwamoto I., Fujino T., Maehata Y., Togami S., Yoshinaga M., Douchi T., (2006) Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer. J. Obstet. Gynaecol. Res. 32: 309–314

    Article  PubMed  CAS  Google Scholar 

  20. Brakora K.A., Lee H., Yusuf R., Sullivan L., Harris A., Colella T., Seiden M.V., (2004) Utility of osteopontin as a biomarker in recurrent epithelial ovarian cancer. Gynecol. Oncol. 93: 361–365

    Article  PubMed  CAS  Google Scholar 

  21. Schorge J.O., Drake R.D., Lee H., Skates S.J., Rajanbabu R., Miller D.S., Kim J.H., Cramer D.W., Berkowitz R.S., Mok S.C., (2004) Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer. Clin. Cancer Res. 10: 3474–3478

    Article  PubMed  CAS  Google Scholar 

  22. Ye B., Skates S., Mok S.C., Horick N.K., Rosenberg H.F., Vitonis A., Edwards D., Sluss P., Han W.K., Berkowitz R.S., Cramer D.W., (2006) Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine. Clin. Cancer Res. 12: 432–441

    Article  PubMed  CAS  Google Scholar 

  23. Benedet J.L., Bender H., Jones H. 3rd, Ngan H.Y., Pecorelli S., (2000) FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int. J. Gynaecol. Obstet. 70: 209–262

    Article  PubMed  CAS  Google Scholar 

  24. McCarty K.S. Jr., Miller L.S., Cox E.B., Konrath J., McCarty Sr. K.S., (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch. Pathol. Lab. Med. 109: 716–721

    PubMed  Google Scholar 

  25. Bradford M.M., (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254

    Article  PubMed  CAS  Google Scholar 

  26. Ue T., Yokozaki H., Kitadai Y., Yamamoto S., Yasui W., Ishikawa T., Tahara E., (1998) Co-expression of osteopontin and CD44v9 in gastric cancer. Int. J. Cancer 79: 127–132

    Article  PubMed  CAS  Google Scholar 

  27. Tuck A.B., Elliott B.E., Hota C., Tremblay E., Chambers A.F., (2000) Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor [14]. J. Cell Biochem. 78: 465–475

    Article  PubMed  CAS  Google Scholar 

  28. Wu Y., Denhardt D.T., Rittling S.R., (2000) Osteopontin is required for full expression of the transformed phenotype by the ras oncogene. Br. J. Cancer 83: 156–163

    Article  PubMed  CAS  Google Scholar 

  29. Adwan H., Bauerle T.J., Berger M.R., (2004) Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells. Cancer Gene. Ther. 11: 109–120

    Article  PubMed  CAS  Google Scholar 

  30. Behrend E.I., Craig A.M., Wilson S.M., Denhardt D.T., Chambers A.F., (1994) Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res. 54: 832–837

    PubMed  CAS  Google Scholar 

  31. O’Neill C.J., Deavers M.T., Malpica A., Foster H., McCluggage W.G., (2005) An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: significantly higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade neoplasms. Am. J. Surg. Pathol. 29: 1034–1041

    PubMed  Google Scholar 

  32. Fisher L.W., Jain A., Tayback M., Fedarko N.S., (2004) Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin. Cancer Res. 10: 8501–8511

    Article  PubMed  CAS  Google Scholar 

  33. Wai P.Y., Kuo P.C., (2004) The role of Osteopontin in tumor metastasis. J. Surg. Res. 121: 228–241

    Article  PubMed  CAS  Google Scholar 

  34. Maki M., Hirota S., Kaneko Y., Morohoshi T., (2000) Expression of osteopontin messenger RNA by macrophages in ovarian serous papillary cystadenocarcinoma: a possible association with calcification of psammoma bodies. Pathol. Int. 50: 531–535

    Article  PubMed  CAS  Google Scholar 

  35. Tiniakos D.G., Yu H., Liapis H., (1998) Osteopontin expression in ovarian carcinomas and tumors of low malignant potential (LMP). Hum. Pathol. 29: 1250–1254

    Article  PubMed  CAS  Google Scholar 

  36. Fujimoto J., Sakaguchi H., Aoki I., Khatun S., Tamaya T., (2001) Clinical implications of expression of vascular endothelial growth factor in metastatic lesions of ovarian cancers. Br. J. Cancer 85: 313–316

    Article  PubMed  CAS  Google Scholar 

  37. Fujimoto J., Aoki I., Toyoki H., Khatun S., Sato E., Sakaguchi H., Tamaya T., (2004) Clinical implications of expression of ETS-1 related to angiogenesis in metastatic lesions of ovarian cancers. Oncology 66: 420–428

    Article  PubMed  CAS  Google Scholar 

  38. Gotoh M., Notoya K., Ienaga Y., Kawase M., Makino H., (2002) Enhancement of osteogenesis in vitro by a novel osteoblast differentiation-promoting compound, TAK-778, partly through the expression of Msx2. Eur. J. Pharmacol. 451: 19–25

    Article  PubMed  CAS  Google Scholar 

  39. Pan H.W., Ou Y.H., Peng S.Y., Liu S.H., Lai P.L., Lee P.H., Sheu J.C., Chen C.L., Hsu H.C., (2003) Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer 98: 119–127

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Hideki Sakaguchi.

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Bao, L.H., Sakaguchi, H., Fujimoto, J. et al. Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers. J Biomed Sci 14, 373–381 (2007). https://doi.org/10.1007/s11373-006-9143-1

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  • DOI: https://doi.org/10.1007/s11373-006-9143-1

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