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Overexpression of human osteopontin increases cell proliferation and migration in human embryo kidney-293 cells

Abstract

Malignant tumors are characterized by dysregulated cell growth and the metastasis of secondary tumors. Numerous studies have documented that osteopontin (OPN) plays a key role in regulating tumor progression and metastasis. Here, we show that the overexpression of OPN in human embryo kidney-293 cells significantly increases both the level of cell proliferation, by provoking the G1/S transition, and the level of cell migration in vitro. These findings suggest that augmented OPN contributes to cell growth and motility. Inhibiting OPN or the pathway it stimulates may therefore represent a novel approach for the treatment of primary tumors and associated metastases.

Abbreviations

ECM:

extracellular matrix

hOPN:

human OPN

IRES:

internal ribosome entry site

OPN:

osteopontin

References

  1. Ramaiah, S.K. and Rittling, S. Pathophysiological role of osteopontin in hepatic inflammation, toxicity, and cancer. Toxicol. Sci. 103 (2008) 4–13.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Rittling, S.R. and Chambers, A.F. Role of osteopontin in tumour progression. Br. J. Cancer 90 (2004) 1877–1881.

    Article  PubMed  CAS  Google Scholar 

  4. Haqq, C., Nosrati, M., Sudilovsky, D., Crothers, J., Khodabakhsh, D., Pulliam, B.L., Federman, S., Miller, J.R.,3rd, Allen, R.E., Singer, M.I., Leong, S.P., Ljung, B.M., Sagebiel, R.W. and Kashani-Sabet, M. The gene expression signatures of melanoma progression. Proc. Natl. Acad. Sci. USA 102 (2005) 6092–6097.

    Article  PubMed  CAS  Google Scholar 

  5. Fedarko, N.S., Jain, A., Karadag, A., Van Eman, M.R. and Fisher, L.W. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin. Cancer Res. 7 (2001) 4060–4066.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Coppola, D., Szabo, M., Boulware, D., Muraca, P., Alsarraj, M., Chambers, A.F. and Yeatman, T.J. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin. Cancer Res. 10 (2004) 184–190.

    Article  PubMed  CAS  Google Scholar 

  8. Rodrigues, L.R., Teixeira, J.A., Schmitt, F.L., Paulsson, M. and Lindmark-Mansson, H. The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol. Biomarkers Prev. 16 (2007) 1087–1097.

    Article  CAS  Google Scholar 

  9. Suzuki, M., Mose, E., Galloy, C. and Tarin, D. Osteopontin gene expression determines spontaneous metastatic performance of orthotopic human breast cancer xenografts. Am. J. Pathol. 171 (2007) 682–692.

    Article  PubMed  CAS  Google Scholar 

  10. Standal, T., Borset, M. and Sundan, A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp. Oncol. 26 (2004) 179–184.

    PubMed  CAS  Google Scholar 

  11. Furger, K.A., Menon, R.K., Tuck, A.B., Bramwell, V.H. and Chambers, A.F. The functional and clinical roles of osteopontin in cancer and metastasis. Curr. Mol. Med. 1 (2001) 621–632.

    Article  PubMed  CAS  Google Scholar 

  12. Chatterjee, S.K. and Zetter, B.R. Cancer biomarkers: knowing the present and predicting the future. Future Oncol. 1 (2005) 37–50.

    Article  PubMed  CAS  Google Scholar 

  13. El-Tanani, M.K., Campbell, F.C., Kurisetty, V., Jin, D., McCann, M. and Rudland, P.S. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev. 17 (2006) 463–474.

    Article  PubMed  CAS  Google Scholar 

  14. Johnston, N.I., Gunasekharan, V.K., Ravindranath, A., O’Connell, C., Johnston, P.G. and El-Tanani, M.K. Osteopontin as a target for cancer therapy. Front Biosci. 13 (2008) 4361–4372.

    Article  PubMed  CAS  Google Scholar 

  15. Mustafa, H., Strasser, B., Rauth, S., Irving, R.A. and Wark, K.L. Identification of a functional nuclear export signal in the green fluorescent protein asFP499. Biochem. Biophys. Res. Commun. 342 (2006) 1178–1182.

    Article  PubMed  CAS  Google Scholar 

  16. Elgavish, A., Prince, C., Chang, P.L., Lloyd, K., Lindsey, R. and Reed, R. Osteopontin stimulates a subpopulation of quiescent human prostate epithelial cells with high proliferative potential to divide in vitro. Prostate 35 (1998) 83–94.

    Article  PubMed  CAS  Google Scholar 

  17. Scatena, M., Almeida, M., Chaisson, M.L., Fausto, N., Nicosia, R.F. and Giachelli, C.M. NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival. J. Cell Biol. 141 (1998) 1083–1093.

    Article  PubMed  CAS  Google Scholar 

  18. Chambers, A.F. and Tuck, A.B. Ras-responsive genes and tumor metastasis. Crit. Rev. Oncog. 4 (1993) 95–114.

    PubMed  CAS  Google Scholar 

  19. Wai, P.Y., Mi, Z., Guo, H., Sarraf-Yazdi, S., Gao, C., Wei, J., Marroquin, C.E., Clary, B. and Kuo, P.C. Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis. Carcinogenesis 26 (2005) 741–751.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Denhardt, D. Osteopontin expression correlates with melanoma invasion. J. Invest. Dermatol. 124 (2005) xvi–xviii.

    Article  PubMed  CAS  Google Scholar 

  22. Geissinger, E., Weisser, C., Fischer, P., Schartl, M. and Wellbrock, C. Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of melanocytes in dermal collagen. Cancer Res. 62 (2002) 4820–4828.

    PubMed  CAS  Google Scholar 

  23. Bogenrieder, T. and Herlyn, M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22 (2003) 6524–6536.

    Article  PubMed  CAS  Google Scholar 

  24. Cook, A.C., Chambers, A.F., Turley, E.A. and Tuck, A.B. Osteopontin induction of hyaluronan synthase 2 expression promotes breast cancer malignancy. J. Biol. Chem. 281 (2006) 24381–24389.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ya-Jun Liu or Wei Tian.

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Liu, YJ., Zhang, DQ., Sui, XM. et al. Overexpression of human osteopontin increases cell proliferation and migration in human embryo kidney-293 cells. Cell Mol Biol Lett 14, 670–678 (2009). https://doi.org/10.2478/s11658-009-0027-z

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  • DOI: https://doi.org/10.2478/s11658-009-0027-z

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