Platelet glycoprotein Ib alpha supports experimental lung metastasis.
The platelet paradigm in hemostasis and thrombosis involves an initiation step that depends on platelet membrane receptors binding to ligands on a damaged or inflamed vascular surface. Once bound to the surface, platelets provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin-rich network produced by coagulation factors. The platelet-specific receptor glycoprotein (GP) Ib-IX, is critical in this process and initiates the formation of a platelet-rich thrombus by tethering the platelet to a thrombogenic surface. A role for platelets beyond the hemostasis/thrombosis paradigm is emerging with significant platelet contributions in both tumorigenesis and inflammation. We have established congenic (N10) mouse colonies (C57BL/6J) with dysfunctional GP Ib-IX receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP Ib-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP Ib-IX contributes to experimental metastasis because a functional absence of GP Ib-IX correlates with a 15-fold reduction in the number of lung metastatic foci using B16F10.1 melanoma cells. The results demonstrate that the extracellular domain of the alpha-subunit of GP Ib is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP Ib-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy.
Jain
Shashank
S
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Zuka
Masahiko
M
Liu
Jungling
J
Russell
Susan
S
Dent
Judith
J
Guerrero
José A
JA
Forsyth
Jane
J
Maruszak
Brigid
B
Gartner
T Kent
TK
Felding-Habermann
Brunhilde
B
Ware
Jerry
J
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D019038:Platelet Glycoprotein GPIb-IX Complex; D021122:Protein Subunits