title: Platelet glycoprotein Ib alpha supports experimental lung metastasis.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Shashank
authors.initials: S
authors.lastname: Jain
authors.forename: Masahiko
authors.initials: M
authors.lastname: Zuka
authors.forename: Jungling
authors.initials: J
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Russell
authors.forename: Judith
authors.initials: J
authors.lastname: Dent
authors.forename: José A
authors.initials: JA
authors.lastname: Guerrero
authors.forename: Jane
authors.initials: J
authors.lastname: Forsyth
authors.forename: Brigid
authors.initials: B
authors.lastname: Maruszak
authors.forename: T Kent
authors.initials: TK
authors.lastname: Gartner
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Felding-Habermann
authors.forename: Jerry
authors.initials: J
authors.lastname: Ware
mesh_terms: 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
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D021122:Protein Subunits