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 alpha6 subunit in human keratinocytes and human
breast cancer cells resulting in increased cell adhesion and
tumor cell invasion. The effect of
TSP-1 on alpha6 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 alpha6 message and
protein in these cells as revealed by differential display, Northern and Western blot analysis and immunohistochemical localization studies. The increased expression of alpha6 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.