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| Article |
| Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells |
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| Alan B Tuck1,2,4, Denise M Arsenault3,4, Frances P O'Malley1, Charulata Hota4, Michael C Ling4, Sylvia M Wilson4 and Ann F Chambers2,4 |
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1Department of Pathology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
2Department of Oncology, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
3Department of Surgery, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada
4London Regional Cancer Centre, London, Ontario, Canada
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Correspondence to: Alan B Tuck, Department of Pathology, London Health Sciences Centre, Victoria Campus, 375 South Street, London, Ontario N6A 4G5, Canada
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| 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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| Keywords |
| osteopontin (OPN); invasion; plasminogen activator; urokinase; mammary epithelial cells; breast cancer |
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| Received 20 May 1998; revised 4 February 1999; accepted 5 March 1999 |
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| 22 July 1999, Volume 18, Number 29, Pages 4237-4246 |
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