Exposure to Alkyllysophospholipids Inhibits in Vitro Invasion of Transitional Cell Carcinoma

Alkyllysophospholipids (ALP) are a group of synthetic analogs of a naturally 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 demonstrated the ability of racemic 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3) to prevent tumor cell invasion when given in noncytotoxic concentrations. Using an in vitro model, we studied the ability of ET-18-O-CH3 to prevent transitional cell carcinoma invasion. Cytostatic activity was determined by clonal growth assay (25,000 cells per plate). Suppression of colony growth was found at concentrations greater than 4 micrograms/ml. of ET-18-O-CH3 in rat and mouse transitional cell carcinoma (TCC) cell lines and greater than 2 micrograms/ml. in a human TCC line. Inhibition of tumor cell invasion was assessed by the effects on cell migration through Matrigel-coated 8 microns-pore polycarbonate 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 highest concentration (4.0 micrograms/ml.). In the human TCC line, invasion was reduced to less than 30% of controls at concentrations as low as 0.5 micrograms/ml. Motility (without invasion) of the human TCC line, as measured by cell migration through the micropore filter without the Matrigel coating, was inhibited at the same concentration of ET-18-O-CH3 found to inhibit invasion. The anti-invasive effect seen with noncytotoxic concentrations of ALP may prove useful in the treatment of transitional cell carcinoma.