Transforming growth factor-beta 1 increases the adhesion of MDA-MB-231 mammary adenocarcinoma cells to the microvascular subendothelium

The increase of tumor cell adhesion to the subendothelium in the presence o f TGF-beta 1 is thought to be mediated by two major events: an enrichment o f extracellular matrix proteins secreted by endothelial cells and an increa se of the integrins on the surface of tumor cells. In this study, we analyz ed the effect of TGF-beta 1 on the adhesion of a mammary adenocarcinoma cel l line (MDA-MB-231) to the matrix of human microvascular endothelial cells (HMEC-1). The adhesion of TGF-beta 1-treated tumor cells to a non-treated m atrix or to purified matrix-proteins was enhanced, while no increase was ob served when non-treated tumor cells were let to adhere to a matrix secreted by HMEC-1 in the presence of the cytokine. Thus, the increase of cell adhe sion was due to the effect of TGF-beta 1 on tumor cells and not to the matr ix enrichment induced by this cytokine. The hyper-adhesion was inhibited by the RGD peptide and EDTA indicating that integrins were involved. Integrin subunits concentrations (alpha 5, alpha v and beta 1) on the surface of TG F-beta 1-treated tumor cells were not modified, while confocal microscopy s howed a reorganization of beta 1 integrin subunits on the cell surface and in the cytoplasm resulting in actin fibers reorganization in the cytoskelet on. This indicates that the enhanced adhesion of TGF-beta 1-treated MDA-MB- 231 cells to the subendothelium is due to a qualitative change of integrins .