The Role of Osteopontin in the Malignancy of Human Breast Carcinoma
Abstract
The objective of this research is to establish whether the secreted phosphoprotein osteopontin (OPN) plays a biological role in the progression of breast carcinoma cells, and to determine the nature of this role, by asking if cell properties and genes associated with malignancy are regulated by OPN. This work makes use of three established mammary epithelial cell lines (21T series) derived from the same patient 21PT cells are immortal but nontumorigenic in the nude mouse; 21NT are weakly tumorigenic, but non-metastatic; and 21MT-1 are tumorigenic, weakly metastatic. In addition, MDA-MB-435 cells are included, representative of a highly malignant, metastatic cell line. We have found that OPN mRNA and protein expression is associated with degree of malignancy in this progression series. Further, we have shown that the more malignant members of this series also bind better to OPN in cell adhesion assays. 21T series and MDA-MB-435 cells have all demonstrated directed migration towards exogenous OPN, and this was associated with increased expression of met (HGF receptor) mRNA and increased sensitivity to HGF. We have found that cell adhesion and migration of 21T series and MDA-MB-435 cells are mediated via cell surface integrins. Interestingly, MDA-MB-435 cells show alphavbeta3 integrin-dependent cell adhesion and migration, whereas 21T series cells exclusively use alpha v Beta 5 and Beta 1 integrins. In cell invasion assays, MDA-MB-435 cells showed a more pronounced response to exogenous OPN than 21PT or 2INT cells. However, invasiveness of 21PT and 21NT cells was upregulated by transfection with a high-expression OPN containing vector, and this was accompanied by increased urokinase expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADB238338
Entities
People
- Alan B. Tuck
- Frances O'malley