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Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells

Oncogene volume 18, pages 4237–4246 (1999)Cite this article

Abstract

Osteopontin (OPN) has been associated with enhanced malignancy in breast cancer, but its functional role in this disease is poorly understood. To study the effect of OPN on cellular invasiveness, basal OPN expression was first assessed in members of a progression series of human mammary epithelial cell lines (21PT: immortalized, non-tumorigenic; 21NT: weakly tumorigenic; 21MT-1: tumorigenic, weakly metastatic; MDA-MB-435 cells: tumorigenic, highly metastatic). The two lines which expressed lowest basal levels of OPN (21PT, 21NT) were then examined for up-regulation of invasive behavior in response to exogenous or transfected (endogenous) OPN. Both 21PT and 21NT showed increased invasiveness through Matrigel when human recombinant (hr)OPN was added to the lower chamber of transwells. Both also showed a cell migration response to hrOPN. Populations of 21PT and 21NT cells stably transfected with an OPN-expression vector showed higher levels of cell invasiness than control vector transfectants. Examination of transfectants for mRNA of a number of secreted proteases showed that only urokinase-type plasminogen activator (uPA) expression was closely associated with OPN expression and cellular invasiveness. Treatment of the parental 21PT and 21NT cells with exogenous hrOPN resulted in increased uPA mRNA expression and increased urokinase activity of the conditioned media. Both increased cell migration and induction of uPA expression are thus potential mechanisms of increased invasiness of breast epithelial cells in response to OPN.

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Acknowledgements

The authors wish to thank Dr Michael Underhill for his kind assistance in the construction of the OPN expression vector. This work was supported by grants from the Canadian Breast Cancer Research Initiative (#8426) and the Breast Cancer Society of Canada. Dr Tuck is supported by a `Career Development' Award from the US Army Breast Cancer Research Program (DOD DAMD17 – 96 – 1 – 6075). The content of this article does not necessarily reflect the position or policy of the US government, and no official endorsement should be inferred.

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Authors and Affiliations

  1. Department of Pathology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada

    Alan B Tuck & Frances P O'Malley

  2. Department of Oncology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada

    Alan B Tuck & Ann F Chambers

  3. Department of Surgery, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada

    Denise M Arsenault

  4. London Regional Cancer Centre, London, Ontario, Canada

    Alan B Tuck, Denise M Arsenault, Charulata Hota, Michael C Ling, Sylvia M Wilson & Ann F Chambers

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Tuck, A., Arsenault, D., O'Malley, F. et al. Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18, 4237–4246 (1999). https://doi.org/10.1038/sj.onc.1202799

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