Gamma linolenic acid regulates gap junction communication in endothelial cells and their interaction with tumour cells.
Tumour-endothelial cell adhesion forms a key role in the establishment of distant metastases. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer polyunsaturated fatty acid (PUFA), on both 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 Lucifer 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-activated endothelial cells, the presence of GLA reduced adhesion of tumour cells to the endothelium. It is concluded that GLA reduces tumour-endothelium adhesion, partly by improved gap junction communications of the endothelium.
Jiang
W G
WG
University Department of Surgery, University of Wales College of Medicine, Cardiff, UK. jiangw@cf.ac.uk
Bryce
R P
RP
Mansel
R E
RE
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018031:Connexin 43 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D007700:Kinetics; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D018031:Connexin 43; D005227:Fatty Acids; D005456:Fluorescent Dyes; D007546:Isoquinolines; D017228:Hepatocyte Growth Factor; D017965:gamma-Linolenic Acid; C017475:lucifer yellow