Platelet glycoprotein VI facilitates experimental lung metastasis in syngenic mouse models.
BACKGROUND
Glycoprotein (GP)VI is a key receptor for collagen on the platelet surface. It is a member of the immunoglobulin superfamily and is uniquely expressed on the surface of platelets, where it is assembled with the immunoreceptor tyrosine activation motif subunit, FcR-gamma. We have previously reported the generation of a murine model of GPVI deficiency that revealed profound defects in collagen-induced platelet aggregation and in platelet activation following adhesion to collagen. Beyond the hemostasis/thrombosis paradigm, platelet receptors are emerging as significant participants in tumorigenesis and inflammation.


OBJECTIVE
In the current study, we have evaluated a role for platelet GPVI in primary tumor growth and experimental metastasis.


METHODS
Primary tumor induction and experimental metastasis assays were performed using syngenic immunocompetent animals and tumor cells derived from the C57BL/6J mouse strain in wild-type (C57BL/6J) and N10 C57BL/6J congenic GPVI-deficient mice.


RESULTS
Using either a Lewis lung carcinoma (D121) or melanoma (B16F10.1) cell line, we observed an approximately 50% reduction in the number of visible tumor foci in GPVI-deficient mice as compared with control C57BL/6J mice. Additional studies were performed to compare the size of subcutaneously implanted tumor cells, that is, primary tumor growth. Here, we observed no noticeable size difference when comparing the presence or absence of platelet GPVI.


CONCLUSIONS
The results demonstrate that the presence of platelet GPVI facilitates experimental tumor metastasis but does not contribute to the growth of primary tumors.
Jain
S
S
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
Russell
S
S
Ware
J
J
D000818:Animals; D001760:Bleeding Time; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000098:blood supply / Q000503:physiopathology / Q000556:secondary*; D045744:Cell Line, Tumor / Q000637:transplantation; D003433:Crosses, Genetic; D005260:Female; D006474:Hemorrhagic Disorders / Q000235:genetics; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000097:blood / Q000098:blood supply / Q000503:physiopathology / Q000556:secondary*; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood / Q000098:blood supply / Q000503:physiopathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013623:Tail; D014185:Transplantation, Isogeneic
D009363:Neoplasm Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C032193:glycoprotein receptor GPIb-IX; C098341:platelet membrane glycoprotein VI