Platelet Glycoprotein Ib Alpha Supports Experimental Lung Metastasis.
From: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: May 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 21
- Pages: 9024-8
- Medium: Print
- Language: English
- Citation (JAMA): Jain Shashank, Zuka Masahiko, Liu Jungling, et al. Platelet Glycoprotein Ib Alpha Supports Experimental Lung Metastasis.. Proc. Natl. Acad. Sci. U.S.A. May 2007;104:9024-8
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.
Mesh Headings (Keywords): Animals, Blood Platelets, Cell Line, Tumor, Disease Models, Animal, Gene Deletion, Humans, Lung Neoplasms, Melanoma, Mice, Mice, Inbred C57BL, Mice, Knockout, Platelet Glycoprotein GPIb-IX Complex, Protein Binding, Protein Subunits
Check for Full Text / PubMed Unique Identifier (PMID): 17494758
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