ANTIINVASIVE EFFECT OF RACEMIC 1-O-OCTADECYL-2-O-METHYLGLYCERO-3-PHOSPHOCHOLINE ON MO4 MOUSE FIBRO-SARCOMA CELLS-INVITRO

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 351-357
Abstract
Alkyl-lysophospholipids were shown to possess antitumoral activity in animal and in human tumors. Among them, racemic 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OCH3) had an antimetastatic effect in experimental tumors. The effect of ET-18-OCH3 on invasion of MO4 mouse fibrosarcoma cells and on cellular activities possibly related to invasion in vitro was studied. Ten .mu.g of ET-18-OCH3 per ml permitted growth of MO4 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 .mu.g of Nocodazole per ml occurred normally in presence of ET-18-OCH3. Invasion was completely inhibited when MO4 cell aggregates were confronted with pre-cultured fragments of embryonic chick cardiac muscle or with fresh embryonic chick lung fragments in culture on gyratory shaker in fluid medium with 10 .mu.g 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 membrane fluidity. Alterations of the MO4 cellular membranes evidently are responsible for the antiinvasive effect of ET-18-OCH3.