Expression of hepatocyte growth factor/scatter factor, its activator, inhibitors and the c-Met receptor in human cancer cells

Hepatocyte growth factor/scatter factor (HGF/SF), a cytokine associated wit h cancer cell migration and invasion, is synthesised as pro-HGF/SF and requ ires activation by factors such as the HGF activator (HGFA). The present st udy examined the expression of HGF/SF, HGFA, the two inhibitors to HGFA act ion known as hepatocyte growth factor activator inhibitors type 1 and 2 (HA I-1 and HAI-2), and the HGF/SF receptor, c-Met. We examined a variety of no rmal and cancer cells, which included breast, prostate, colon, bladder, liv er, lung, and pancreatic cancer cell lines. The cell lines all displayed di fferent patterns of expression, and in some of the cancer cell lines the co ncomitant expression of the HGF/SF, c-Met, HGFA and HAI genes was observed. The only cell line to produce a significant amount of HGF/SF was the human fibroblasts (MRC-5) which also co-expressed the c-Met and HGFA genes to al low autocrine regulation of HGF/SF stimulation, and importantly displayed l ittle or no inhibitor presence to suppress the biological function of HGF/S F. The highly invasive breast cancer cells (MDA MB-231) expressed large amo unts of both c-Met and HGFA, to enable maximum influence from HGF/SF and di d not express the HAI-1 gene at all, which suggests a shift in the activati on-inhibition balance to enhance metastatic potential. In contrast, the bre ast cancer cells of low invasive nature (MCF-7) displayed a low level of c- Met and HGFA expression, while expressing the HAI genes to a high degree. H owever, there was no correlation between HAI-1 and HAI-2 expression. Intere stingly, there appeared to be an inverse correlation between the degree of HGFA and HAI-1 expression, which may influence the metastatic ability of th e cancer cells. This study has shown that c-Met, HGF/SF and its activator a nd inhibitors are expressed in different patterns in cancer cells and in no rmal cells. The balance between HGF/SF activation and HGFA inhibition is cr itical to the metastatic potential of the tumour cells, and the invasive na ture of the cancer cell lines correlated to the degree of c-Met and/or HGFA presence along with HAI-1 expression.