Lipoxygenase products regulate IRGpIIb/IIIa receptor mediated adhesion of tumor cells to endothelial cells, subendothelial matrix and fibronectin |
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Authors: | K V Honn I M Grossi L A Fitzgerald L A Umbarger C A Diglio J D Taylor |
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Institution: | Department of Radiation Oncology, Wayne State University, Detroit, MI 48202. |
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Abstract: | Tumor cell adhesion to endothelial cells, subendothelial matrix, and fibronectin is stimulated by the lipoxygenase metabolite of arachidonic acid, 12(S)-HETE, but not by 12(R)-HETE, 5-HETE or 15-HETE. Adhesion is also stimulated by the phorbol ester TPA, an effect inhibited by lipoxygenase but not cyclooxygenase inhibitors. TPA and 12(S)-HETE mediated adhesion is due, in part, to an integrin receptor (i.e., IRGpIIb/IIIa) related to the platelet glycoprotein IIb/IIIa complex and is inhibited by specific monoclonal and polyclonal antibodies against platelet IIb/IIIa. TPA and 12(S)-HETE stimulated adhesion is also inhibited by a lipoxygenase product of linoleic acid; i.e., 13-HODE. These results suggest bidirectional control of tumor cell adhesion by lipoxygenase products of arachidonic acid (increase) and linoleic acid (decrease). |
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