Bidirectional control of membrane expression and/or activation of the tumor cell IRGpIIb/IIIa receptor and tumor cell adhesion by lipoxygenase products of arachidonic acid and linoleic acid.
Lewis lung carcinoma cells express a plasma membrane receptor (i.e., IRGpIIb/IIIa) which is immunologically and functionally related to the platelet aggregation receptor complex (i.e., GpIIb/IIIa). Both fluorescence microscopy and flow cytometric analysis reveal that surface expression and/or activation of this tumor cell receptor is enhanced by a phorbol ester [i.e., 12-O-tetradecanoylphorbol-13-acetate (TPA)] and a lipoxygenase metabolite of arachidonic acid; 12-hydroxyeicosatetraenoic acid (i.e., 12-HETE). TPA-enhanced expression appears to be mediated by a lipoxygenase metabolite, as this effect can be reversed by lipoxygenase inhibitors but not by cyclooxygenase inhibitors. In parallel with these results both TPA and 12(S)-HETE [but not 12(R)-HETE] enhance tumor cell adhesion to endothelial cells, subendothelial matrix and fibronectin, but not to type IV collagen. TPA-enhanced adhesion can be reduced by lipoxygenase inhibitors but not by cyclooxygenase inhibitors and in addition, stimulated adhesion can be blocked by pretreatment of tumor cells with specific polyclonal or monoclonal antibodies which react against IRGpIIb/IIIa. 12(S)-HETE-enhanced adhesion can also be inhibited by these same antibodies. In contrast, a lipoxygenase product of linoleic acid, 13(S)-hydroxyoctadecadienoic acid, inhibited TPA and 12(S)-HETE-enhanced tumor cell adhesion to endothelial cells, subendothelial matrix, and fibronectin. These results suggest that (a) IRGpIIb/IIIa is a multifunctional receptor which mediates tumor cell adhesion to a variety of biological substrata, (b) TPA enhances surface expression and/or activation of this receptor possibly via a lipoxygenase metabolite of arachidonic acid, and (c) these effects are opposed by a lipoxygenase metabolite of linoleic acid.
Grossi
I M
IM
Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202.
Fitzgerald
L A
LA
Umbarger
L A
LA
Nelson
K K
KK
Diglio
C A
CA
Taylor
J D
JD
Honn
K V
KV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002462:Cell Membrane / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007536:Isomerism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D008175:Lung Neoplasms / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D010980:Platelet Membrane Glycoproteins; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003094:Collagen; D019787:Linoleic Acid; D008084:Lipoxygenase; D013755:Tetradecanoylphorbol Acetate