UNSATURATED FATTY-ACID EFFECTS ON HUMAN BREAST-CANCER CELL-ADHESION

Polyunsaturated fatty acids influence several steps involved in metast asis/formation in animal tumor models. During the process of metastasi s from the primary site, tumor cells adhere to the endothelium and und erlying basement membrane before extravasation and secondary growth. T he purpose of this study was to determine the effect of unsaturated fa tty acids on adhesion of human breast cancer cell lines to components of the basement membrane. Cells were cultured in low-serum medium for five days with or without added unsaturated fatty acids. Adhesion assa ys were conducted by incubating cells with basement membrane substrate s coated on 96-well plates, washing to remove nonadherent cells, and s taining adherent cells with crystal violet. Linoleic acid (LA) and eic osapentaenoic acid increased adhesion of the metastatic cell line MDA- MB-231 to Matrigel and type IV collagen, while eicosapentaenoic acid d ecreased adhesion of the less metastatic cell line SK-BR-3 to these tw o basement membrane substrates. Oleic acid increased adhesion of MDA-M B-231 cells to Matrigel and fibronectin. Nordihydroguaiaretic acid and high concentrations of indomethacin, each of which inhibits the lipox ygenase pathway of arachidonate metabolism, were effective in reversin g the stimulatory effect of LA on MDA-MB-231 cell adhesion. A protein kinase C inhibitor likewise suppressed the increase in adhesion observ ed when MDA-MB-231 cells were incubated in media with added LA. Unsatu rated fatty acids modified the adhesive properties of human breast can cer cell lines in vitro, and LA appeared to increase human breast canc er cell adhesion to extracellular matrix components by activating lipo xygenase and/or protein kinase C pathways.