Thrombospondin-1 (TSP-1) Stimulates Expression of Integrinα6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion

Thrombospondin-1 (TSP-1) is involved in a variety of different cellular processes including cell adhesion, tumor progression, and angiogenesis. This paper reports the novel finding that TSP-1 upregulates integrin α 6 subunit in human keratinocytes and human breast cancer cells resulting in increased cell adhesion and tumor cell invasion. The effect of TSP-1 on α 6 subunit expression was examined in human keratinocytes and breast adenocarcinoma cell lines (MDA-MB-231) treated with TSP-1 and in TSP-1 stably transfected breast cancer cells. TSP-1 upregulated α 6 message and protein in these cells as revealed by differential display, Northern and Western blot analysis and immunohistochemical localization studies. The increased expression of α 6 was shown to mediate adhesion and invasion of these cells to laminin, a major component of the basement membrane and extracellular matrix (ECM). These data suggest that TSP-1 plays an integral role in the attachment of cells to the ECM facilitating cell motility and angiogenesis.