EXPOSURE TO ALKYLLYSOPHOSPHOLIPIDS INHIBITS IN-VITRO INVASION OF TRANSITIONAL-CELL CARCINOMA

Alkyllysophospholipids (ALP) are a group of synthetic analogs of a nat urally occurring 2-lysophosphocholine. They are directly cytotoxic to a variety of neoplastic cell lines and can modulate the activation of macrophages against tumor cells. Moreover, recent reports have demonst rated the ability of racemic 1-octadecyl-2-methyl-sn-glycero-3-phospho choline (ET-18-O-CH3) to prevent tumor cell invasion when given in non cytotoxic concentrations. Using an in vitro model, we studied the abil ity of ET-18-O-CH3 to prevent transitional cell carcinoma invasion. Cy tostatic activity was determined by clonal growth assay (25,000 cells per plate). Suppression of colony growth was found at concentrations g reater than 4 mu g./ml. of ET-18-O-CH3 in rat and mouse transitional c ell carcinoma (TCC) cell lines and greater than 2 mu g./ml. in a human TCC line. Inhibition of tumor cell invasion was assessed by the effec ts on cell migration through Matrigel(R)-coated 8 mu m.-pore polycarbo nate filters (using 1 x 10(5) cells per chamber). Invasion was reduced to 50 to 70% of controls in both the mouse and rat TCC lines at the h ighest concentration (4.0 mu g./ml.). In the human TCC line, invasion was reduced to less than 30% of controls at concentrations as low as 0 .5 mu g./ml. Motility (without invasion) of the human TCC line, as mea sured by cell migration through the micropore filter without the Matri gel(R) coating, was inhibited at the same concentration of ET-18-O-CH3 found to inhibit invasion. The anti-invasive effect seen with noncyto toxic concentrations of ALP may prove useful in the treatment of trans itional cell carcinoma.