Angiogenic capacity and lung-colonizing potential in vivo is increased in weakly metastatic B16F1 cells and decreased in highly metastatic BL6 cells by phorbol esters.

The development of tumor metastasis is a multistep process. Key aspects of this process are the interaction of tumor cells with the extracellular matrix, digestion of, and motility through the basement membrane and the induction of angiogenesis. In this study, we analysed the effects of a low dose of TPA (12-tetradecanoylphorbol-13-acetate; 0.1 microM on angiogenesis, proteolytic activity and lung colonizing potential of both weakly metastatic B16F1 cells and highly metastatic BL6 murine melanoma cells. Our results demonstrated opposite effects of TPA in the two cell lines. TPA-treated B16F1 cells showed enhanced release of basic FGF (bFGF) and vascular endothelial growth factor (VEGF) and increased angiogenic capacity and lung colony formation in vivo. In contrast, TPA-treated BL6 cells demonstrated a dramatic reduction of angiogenic and gelatinolytic activity and metastatic capacity. However, both cell lines showed an induction of VEGF as well as bFGF expression by TPA treatment suggesting that in BL6 cells antagonistic factors, inhibiting the angiogenic and metastatic capacity, are induced by this treatment.