Secretion of hepatocyte growth factor and vascular endothelial growth factor during uveal melanoma-monocyte in vitro interactions

Host-tumour interactions in uveal melanoma, and their involvement in the biological events leading to metastasis and eventually mortality, are not well understood. It is known that uveal melanoma disseminates predominantly via a haematogenous route with metastasis developing primarily in the liver. Therefore, cytokines involved in angiogenesis, such as vascular endothelial growth factor (VEGF), and those expressed in large quantities within the liver, such as hepatocyte growth factor (HGF), are of particular interest in uveal melanoma research. This study investigated the levels of HGF and VEGF in monocyte and uveal melanoma-conditioned medium. Five human uveal melanoma cell lines and one monocyte cell line were seeded in six-well plates. After 18 h, melanoma-conditioned medium (MCM) was placed on the monocyte cell line and monocyte-conditioned medium (MoCM) was placed on each uveal melanoma cell line. Tumour cells and monocytes incubated in fresh, as opposed to conditioned, medium after 18 h were used as controls. VEGF and HGF levels were determined by immunoassay prior to media transfer and 6, 12, 24 and 36 h thereafter. Both cytokines showed an upregulation of expression from all cells after incubation in conditioned medium. 28SC incubated in MCM expressed higher levels of the given cytokines than did uveal melanoma cells incubated in MoCM. In addition, each cell line exhibited a distinct pattern of expression, with individual cell lines exhibiting different peak levels of cytokine production at different time points. These results offer insight into the upregulation of VEGF and HGF, which may play a role in tumour-host cell interactions.