GAMMA-LINOLENIC ACID REGULATES GAP JUNCTION COMMUNICATION IN ENDOTHELIAL-CELLS AND THEIR INTERACTION WITH TUMOR-CELLS

Tumour-endothelial cell adhesion forms a key role in the establishment of distant metastases. This study examined the effect of gamma linole nic acid (GLA), an anti-cancer polyunsaturated fatty acid (PUFA), on b oth the gap junction communication of human vascular endothelial cells and tumour cell-endothelial interactions. By using scrape loading of Lucifer yellow dye, we showed that GLA at non-toxic levels increased L ucifer yellow transfer, indicating improved gap junction communication . The fatty acid also corrected the communication that was reduced by the mitogenic and motogenic factor HGF/SF. GLA inhibited the tyrosine phosphorylation of connexin-43, a protein that formed gap junction in this cell. When human tumour cells were added to quiescent or HGF/SF-a ctivated endothelial cells, the presence of GLA reduced adhesion of tu mour cells to the endothelium. It is concluded that GLA reduces tumour -endothelium adhesion, partly by improved gap junction communications of the endothelium.