Antiinvasive Effect of Racemic l-O-Octadecyl-2-O-methylglycero-S- phosphocholine on MO4 Mouse Fibrosarcoma Cells in V/tro1

Alkyl-lysophospholipids have been shown to possess antitumoral activity in animal and in human tumors. Among them, racemic 1-O-œtadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OCH3) had an antimetastatic effect in experimental tu mors. We investigated the effect of ET-18-OCH3 on invasion of MO4 mouse fibrosarcoma cells and on cellular activities possibly related to invasion In vitro. Ten /¿gof ET-18-OCH3 per ml per mitted growth of M04 cells to about 75% of controls and slightly reduced trypan blue exclusion. Directional migration inferred from the area covered by MO4 cells that had migrated from an aggregate on glass was not affected. Reassembly of microtubules after treatment with 1 /¿gof Nocodazole per ml occurred normally in presence of ET-18-OCH3. Invasion was completely inhibited when MO«cell aggregates were confronted with precultured fragments of embryonic chick cardiac muscle or with fresh embryonic chick lung fragments in culture on gyratory shaker in fluid medium with 10 /ig of ET-18-OCH3 per ml. These experiments showed that ET-18-OCH3, in contrast with microtubule inhibitors, interfered with invasion of MO4 cells in vitro at concentrations that permitted growth and directional migration of MO4 cells. Fluorescence polarization studies with the lipophylic probe diphenylhexatriene indicated that the antiinvasive effect of ET-18-OCH3 was accompanied by an overall increase of mem brane fluidity. We tentatively concluded that alterations of the MO4 cellular membranes are responsible for the antiinvasive effect of ET-18-OCH3.