HEXADECYLPHOSPHOCHOLINE INHIBITS INVASION OF MOUSE T-CELL LYMPHOMA-CELLS IN 2 DIFFERENT INVASION ASSAYS

Hexadecylphosphocholine (HePC), an ether lipid analogue, is a new anti neoplastic drug which has been shown to exert a remarkable antiprolife rative effect in vitro and in vivo. The signal transduction pathway an d the phospholipid synthesis are thought to be the main putative molec ular targets of HePC, yet the exact mechanism of action is still uncle ar To investigate the antiinvasive activity of HePC on a mouse T-cell lymphoma cell line (BW-O-Li1), we used a type I collagen gel and devit alized dermis as substrate to evaluate the migration of BW-O-Li1 after exposure to HePC. BW-O-Li1 cells were exposed for 24h to a non-cytoto xic (10 mu M) as well as to cytotoxic concentrations of HePC. Afterwar ds, BW-O-Li1 cells were seeded on top of a reconstituted collagen gel layer or pippeted into a steel ring placed on the dermal site of a dev italized dermis. Lymphoma cells, which invaded the collagen layer were counted by light microscopy, invasion into devitalized dermis was mea sured by an image analysis system. Compared to unexposed cells, invasi on into the collagen gel differed significantly even at 10 mu M HePC, whereas the absolute number of invading cells, independently of the He PC concentration, showed no difference in the amount of counted cells. Migration into devitalized dermis was significantly reduced for 10 mu M and 40 mu M HePC. These data show that complementary information ca n be obtained by application of the two invasion assays and that the a ntiinvasive effect of HePC emerges at non-cytotoxic concentrations of the substance.