Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells
| Autor: | Sylvia M. Wilson, Frances P. O'Malley, Michael C Ling, Alan B. Tuck, Ann F. Chambers, Denise M Arsenault, Charulata Hota |
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| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
medicine.medical_specialty Recombinant Fusion Proteins Sialoglycoproteins Cell Breast Neoplasms Transfection medicine.disease_cause stomatognathic system Internal medicine Tumor Cells Cultured Genetics medicine Humans Neoplasm Invasiveness Breast RNA Messenger RNA Neoplasm Osteopontin Neoplasm Metastasis Molecular Biology Cell Line Transformed Matrigel biology Epithelial Cells Cell migration Urokinase-Type Plasminogen Activator Extracellular Matrix Neoplasm Proteins Gene Expression Regulation Neoplastic Drug Combinations Cell Transformation Neoplastic Endocrinology medicine.anatomical_structure Cell culture Culture Media Conditioned Disease Progression Cancer research biology.protein Female Proteoglycans Collagen Laminin Carcinogenesis Plasminogen activator |
| Zdroj: | Oncogene. 18:4237-4246 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1202799 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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