The FASEB Journal, Vol 3, 2285-2293, Copyright © 1989 by The Federation of American Societies for Experimental Biology

REVIEWS

Enhanced tumor cell adhesion to the subendothelial matrix resulting from 12(S)-HETE-induced endothelial cell retraction

KV Honn, IM Grossi, CA Diglio, M Wojtukiewicz and JD Taylor
Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202.

A 12-lipoxygenase metabolite of arachidonic acid, 12(S)- hydroxyeicosatetraenoic acid (12[S]-HETE), which is produced by platelets and tumor cells, was tested for its ability to induce retraction of endothelial cell monolayers. The induction of endothelial cell retraction is a critical step in tumor cell metastasis. Endothelial cells demonstrated reversible retraction in response to 12(S)-HETE, but did not respond to the stereoisomer 12(R)-HETE or to unrelated 5-lipoxygenase (i.e., 5[S]-HETE) or 15-lipoxygenase (i.e., 15[S]-HETE) metabolites. Endothelial cells did not demonstrate loss of viability in response to 12(S)-HETE. The induction of retraction was both dose and time dependent. Scanning electron microscopy confirmed that 12(S)-HETE induced endothelial cell retraction and revealed collapsed filopodia on their surface, the appearance of spaces between endothelial cells and the underlying subendothelial matrix, in addition to large gaps between adjacent endothelial cells. Tumor cell adhesion to endothelial cell monolayers was enhanced 1 h after pretreatment of monolayers with 12(S)-HETE but not after pretreatment with other lipoxygenase metabolites. Tumor cell adhesion to endothelial cell monolayers 36 h after pretreatment with 12(S)-HETE was not different from adhesion to untreated monolayers. Therefore we suggest that 12(S)- HETE generated during tumor cell-platelet-endothelial cell interactions may induce reversible endothelial cell retraction, allowing tumor cell access to the subendothelial matrix, which is a critical step in their eventual extravasation from the microvasculature during hematogenous metastasis.

This article has been cited by other articles:

				J. Jankun, A. M. Aleem, S. Malgorzewicz, M. Szkudlarek, M. I. Zavodszky, D. L. DeWitt, M. Feig, S. H. Selman, and E. Skrzypczak-Jankun Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells Mol. Cancer Ther., May 1, 2006; 5(5): 1371 - 1382. [Abstract] [Full Text] [PDF]

				H. Wang, W. Fu, J. H. Im, Z. Zhou, S. A. Santoro, V. Iyer, C. M. DiPersio, Q.-C. Yu, V. Quaranta, A. Al-Mehdi, et al. Tumor cell {alpha}3{beta}1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis J. Cell Biol., March 15, 2004; 164(6): 935 - 941. [Abstract] [Full Text] [PDF]

				T.-H. Lee, H. K. Avraham, S. Jiang, and S. Avraham Vascular Endothelial Growth Factor Modulates the Transendothelial Migration of MDA-MB-231 Breast Cancer Cells through Regulation of Brain Microvascular Endothelial Cell Permeability J. Biol. Chem., February 7, 2003; 278(7): 5277 - 5284. [Abstract] [Full Text] [PDF]

				D. NIE, K. TANG, K. SZEKERES, L. LI, and K. V. HONN Eicosanoid Regulation of Angiogenesis in Human Prostate Carcinoma and Its Therapeutic Implications Ann. N.Y. Acad. Sci., April 1, 2000; 905(1): 165 - 176. [Abstract] [Full Text] [PDF]

				R. Natarajan, R. Esworthy, W. Bai, J.-L. Gu, S. Wilczynski, and J. Nadler Increased 12-Lipoxygenase Expression in Breast Cancer Tissues and Cells. Regulation by Epidermal Growth Factor J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1790 - 1798. [Abstract] [Full Text] [PDF]

				D. Tang, C. Diglio, R Bazaz, and K. Honn Transcriptional activation of endothelial cell integrin alpha v by protein kinase C activator 12(S)-HETE J. Cell Sci., January 7, 1995; 108(7): 2629 - 2644. [Abstract] [PDF]