INHIBITION OF INDUCED ANGIOGENESIS IN A HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE BY ET-18-OCH3

Alkyl-lysophospholipids are a group of anticancer compounds that have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. One of these compounds, ET-18-OCH3, has b een used for purging bone marrow of cancer cells in phase I clinical t rials. Tumor-induced angiogenesis has been directly correlated with tu mor growth and metastasis. In this study, we examined the effect ET-18 -OCH3 has on a human microvascular endothelial cell line (HMEC-1), inc luding the following functions: angiogenesis, cell-adhesion molecule e xpression, and cell-junction integrity. We found that ET-18-OCH3 (in v itro) reversibly inhibited induced angiogenesis at levels that did not affect viability. At lower concentrations, ET-18-OCH3 down-regulated the expression of cell-adhesion molecules and affected the integrity o f cell-to-cell junctions. This observation demonstrates this versatile family of compounds to have additional targets of action.