| Autor: |
Anna-Karin Olsson, Agneta Siegbahn, Wilhelm Jahnen-Dechent, Kristian Pietras, Helena Åkerud, Taina Pihlajaniemi, Bo Nilsson, Rolf Bjerkvig, Jian Wang, Osama Hamad, Marja-Riitta Väisänen, Timo Väisänen, Karin Kårehed, Anna Dimberg, Maria Ringvall, Åsa Thulin |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1541-7786.c.6541972.v1 |
| Popis: |
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 Zn2+. 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. (Mol Cancer Res 2009;7(11):1792–802) |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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