• Journal Article

12(S)-HETE promotes tumor-cell adhesion by increasing surface expression of alpha V beta 3 integrins on endothelial cells

Citation

Tang, D. G., Grossi, I., Chen, Y. Q., Diglio, C. A., & Honn, K. V. (1993). 12(S)-HETE promotes tumor-cell adhesion by increasing surface expression of alpha V beta 3 integrins on endothelial cells. International Journal of Cancer, 54(1), 102-111.

Abstract

The present work was undertaken to investigate the regulatory role of 12(S)-HETE, a lipoxygenase metabolite of arachidonic acid, in the surface expression of alpha v beta 3 integrin receptors in endothelial cells (rat aortic endothelial cells, or RAEC). Several monoclonal and polyclonal antibodies localized alpha v beta 3 in focal adhesions in both subconfluent and post-confluent RAEC. RAEC alpha v beta 3 integrins were further characterized by immunoblotting and immunoprecipitation. 12(S)-HETE, but not 12(R)-HETE or other lipoxygenase-derived hydroxy fatty acids, induced a dose-dependent increase in alpha v beta 3 surface expression in RAEC, which was antagonized by prostacyclin or its analog iloprost as well as by 13-HODE, a 15-lipoxygenase product of linoleic acid. 12(S)-HETE promoted RAEC adhesion to vitronectin, an effect inhibited by antibodies against alpha v beta 3. 12(S)-HETE also promoted tumor-cell (W256 carcinosarcoma) adhesion to vitronectin, which was inhibited by various antibodies against alpha IIb beta 3 but not by an antibody against alpha v. W256 adhesion to 12(S)-HETE-treated RAEC demonstrated a significant increase, which was inhibited by anti-alpha v, -beta 3, or -alpha v beta 3 antibodies and by 13-HODE. Western blotting, immunoprecipitation and reverse transcription-polymerase chain reaction indicated that W256 carcinosarcoma cells expressed alpha IIb beta 3 integrins but not alpha v beta 3. The results suggest that the lipoxygenase metabolites [i.e., 12(S)-HETE and 13-HODE] play a significant role in modulating tumor-cell interactions with endothelium by enhancing endothelial cell integrin (e.g., alpha v beta 3) expression