Is there a role for the tumor cell integrin alpha IIb beta 3 and cytoskeleton in tumor cell-platelet interaction?
In vitro tumor cell-platelet interaction was examined using B16 amelanotic (B16a) melanoma cells. These tumor cells express the alpha IIb beta 3-type cytoadhesin. Aggregation studies demonstrated that tumor cell surface alpha IIb beta 3 mediates the recognition of platelets since pretreatment of tumor cells with antibody against alpha IIb beta 3 prevents platelet-tumor cell interaction as well as platelet activation measured by aggregometry, platelet eicosanoid metabolism and ultrastructural analysis. In B16a cells, disruption of the microfilaments and intermediate filaments inhibits mobility of alpha IIb beta 3 on the cell surface. Microtubules do not play a role in receptor mobility, because B16a cells do not possess well-defined microtubules in interphase and colchicine does not affect receptor mobility. Disruption of microfilaments or intermediate filaments results in an inhibition of tumor cell-platelet interaction as evidenced by aggregometry studies and ultrastructural analysis. We suggest that platelet interaction with tumor cells begins with alpha IIb beta 3-mediated receptor recognition followed by not only platelet activation but also microfilament- and vimentin intermediate filament-dependent tumor cell activation.
Department of Pathology, VA Medical Center, Allen Park, MI 48101.
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H
Chopra
J
J
Timar
X
X
Rong
I M
IM
Grossi
J S
JS
Hatfield
S E
SE
Fligiel
C A
CA
Finch
J D
JD
Taylor
K V
KV
Honn
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007382:Intermediate Filaments / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013928:Thromboxane A2 / Q000032:analysis; D014404:Tubulin / Q000032:analysis; D014746:Vimentin / Q000032:analysis
D006893:Hydroxyeicosatetraenoic Acids; D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014404:Tubulin; D014746:Vimentin; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid