| First Author | Thulin A | Year | 2009 |
| Journal | Mol Cancer Res | Volume | 7 |
| Issue | 11 | Pages | 1792-802 |
| PubMed ID | 19903770 | Mgi Jnum | J:205242 |
| Mgi Id | MGI:5544405 | Doi | 10.1158/1541-7786.MCR-09-0094 |
| Citation | Thulin A, et al. (2009) Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein. Mol Cancer Res 7(11):1792-802 |
| abstractText | The angiogenesis inhibitor histidine-rich glycoprotein (HRG) constitutes one of several examples of molecules regulating both angiogenesis and hemostasis. The antiangiogenic properties of HRG are mediated via its proteolytically released histidine- and proline-rich (His/Pro-rich) domain. Using a combination of immunohistochemistry and mass spectrometry, we here provide biochemical evidence for the presence of a proteolytic peptide, corresponding to the antiangiogenic domain of HRG, in vivo in human tissue. This finding supports a role for HRG as an endogenous regulator of angiogenesis. Interestingly, the His/Pro-rich peptide bound to the vessel wall in tissue from cancer patients but not to the vasculature in tissue from healthy persons. Moreover, the His/Pro-rich peptide was found in close association with platelets. Relesate from in vitro-activated platelets promoted binding of the His/Pro-rich domain of HRG to endothelial cells, an effect mediated by Zn(2+). Previous studies have shown that zinc-dependent binding of the His/Pro-rich domain of HRG to heparan sulfate on endothelial cells is required for inhibition of angiogenesis. We describe a novel mechanism to increase the local concentration and activity of an angiogenesis inhibitor, which may reflect a host response to counteract angiogenesis during pathologic conditions. Our finding that tumor angiogenesis is elevated in HRG-deficient mice supports this conclusion. |
