Regulation of endothelial CD44 expression and endothelium-tumour cell interactions by hepatocyte growth...

Cancer metastasis involves the passage of tumour cells into and out of blood or lymphatic circulatory systems and requires their interaction with the endothelial cells lining these vessels. Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional protein that enhances tumour cell motility and extracellular matrix invasion and has been implicated as a mediator of metastasis. In this study, we have investigated the effect of HGF/SF on tumour cell-endothelial cell interactions. A fluorescent tumour cell-endothelial cell attachment assay demonstrated that, following endothelial monolayer stimulation with HGF/SF, tumour cell attachment to endothelium is increased. Addition of anti-CD44 antibodies in this assay inhibited the effects of HGF/SF. Western blotting studies showed that HGF/SF increased expression of the adhesion molecule CD44 in endothelial cells. These results were confirmed by both immunohistochemical staining and a cell-surface adhesion molecule ELISA. These results suggest that HGF/SF plays a key role in the initial adhesion mechanism between tumour cells and endothelial cells via up-regulation of CD44.