Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles
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 as...
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| Veröffentlicht in: | PloS one 2014-04, Vol.9 (4), p.e95983-e95983 |
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| creator | Munster, Michal Fremder, Ella Miller, Valeria Ben-Tsedek, Neta Davidi, Shiri Scherer, Stefan J Shaked, Yuval |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0095983 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0095983</identifier><identifier>PMID: 24752333</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Angiogenesis Inhibitors - therapeutic use ; Animals ; Antiangiogenics ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Agents - therapeutic use ; Bevacizumab ; Biology and Life Sciences ; Blood platelets ; Bone marrow ; Boyden chamber ; Breast cancer ; Breast carcinoma ; Cancer cells ; Cancer therapies ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell-Derived Microparticles ; Chemotherapy ; Colonization ; Drugs ; Exposure ; Flow cytometry ; Homing ; Human Umbilical Vein Endothelial Cells - cytology ; Humans ; Medicine ; Medicine and Health Sciences ; Mice ; Microparticles ; Neovascularization, Pathologic - drug therapy ; Neutralization ; Pharmacology ; Tumor cells ; Tumors ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e95983-e95983</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Munster et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Munster et al 2014 Munster et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-dda1a727a831c376fc04983271c08be358bce2e2385a04c6aca9e5c3ea748e843</citedby><cites>FETCH-LOGICAL-c692t-dda1a727a831c376fc04983271c08be358bce2e2385a04c6aca9e5c3ea748e843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994111/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994111/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24752333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bertolini, Francesco</contributor><creatorcontrib>Munster, Michal</creatorcontrib><creatorcontrib>Fremder, Ella</creatorcontrib><creatorcontrib>Miller, Valeria</creatorcontrib><creatorcontrib>Ben-Tsedek, Neta</creatorcontrib><creatorcontrib>Davidi, Shiri</creatorcontrib><creatorcontrib>Scherer, Stefan J</creatorcontrib><creatorcontrib>Shaked, Yuval</creatorcontrib><title>Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Angiogenesis Inhibitors - therapeutic use</subject><subject>Animals</subject><subject>Antiangiogenics</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Bevacizumab</subject><subject>Biology and Life Sciences</subject><subject>Blood platelets</subject><subject>Bone marrow</subject><subject>Boyden chamber</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell-Derived Microparticles</subject><subject>Chemotherapy</subject><subject>Colonization</subject><subject>Drugs</subject><subject>Exposure</subject><subject>Flow cytometry</subject><subject>Homing</subject><subject>Human Umbilical Vein Endothelial Cells - 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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. 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| subjects | Analysis Angiogenesis Angiogenesis Inhibitors - therapeutic use Animals Antiangiogenics Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Agents - therapeutic use Bevacizumab Biology and Life Sciences Blood platelets Bone marrow Boyden chamber Breast cancer Breast carcinoma Cancer cells Cancer therapies Cell Line, Tumor Cell Movement - drug effects Cell-Derived Microparticles Chemotherapy Colonization Drugs Exposure Flow cytometry Homing Human Umbilical Vein Endothelial Cells - cytology Humans Medicine Medicine and Health Sciences Mice Microparticles Neovascularization, Pathologic - drug therapy Neutralization Pharmacology Tumor cells Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism |
| title | Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles |
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