期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 21, 页码 9024-9028出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700625104
关键词
adhesion; tumor; hemostasis; knockout; melanoma
资金
- NCI NIH HHS [R01 CA095458, CA095458] Funding Source: Medline
- NHLBI NIH HHS [HL50545, R01 HL050545, R01 HL050545-14] Funding Source: Medline
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) lb-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-1X receptors in our laboratory that allow us an opportunity to examine the relevance of platelet GP lb-IX in syngeneic mouse models of experimental metastasis. Our results demonstrate platelet GP lb-IX contributes to experimental metastasis because a functional absence of GP lb-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 a-subunit of GP lb is the structurally relevant component of the GP Ib-IX complex contributing to metastasis. Our results support the hypothesis that platelet GP lb-IX functions that support normal hemostasis or pathologic thrombosis also contribute to tumor malignancy.
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