title: Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles.
abstract: Tumor derived microparticles (TMPs) have recently been shown to contribute to tumor re-growth partially by inducing the mobilization and tumor homing of specific bone marrow derived pro-angiogenic cells (BMDCs). Since antiangiogenic drugs block proangiogenic BMDC mobilization and tumor homing, we asked whether TMPs from cells exposed to an antiangiogenic drug may affect BMDC activity and trafficking. Here we show that the level of VEGF-A is reduced in TMPs from EMT/6 breast carcinoma cells exposed to the anti-VEGF-A antibody, B20. Consequently, these TMPs exhibit reduced angiogenic potential as evaluated by a Matrigel plug and Boyden chamber assays. Consistently, BMDC mobilization, tumor angiogenesis, microvessel density and BMDC-colonization in growing tumors are reduced in mice inoculated with TMPs from B20-exposed cells as compared to mice inoculated with control TMPs. Collectively, our results suggest that the neutralization of VEGF-A in cultured tumor cells can block TMP-induced BMDC mobilization and colonization of tumors and hence provide another mechanism of action by which antiangiogenic drugs act to inhibit tumor growth and angiogenesis.
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Munster
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Fremder
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Valeria
authors.initials: V
authors.lastname: Miller
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Ben-Tsedek
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Davidi
authors.affiliation: Hoffmann La Roche, Basel, Switzerland.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Scherer
authors.affiliation: Department of Molecular pharmacology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Shaked
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D055252:Cell-Derived Microparticles; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
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