Chemotherapy Enhances Metastasis Formation via VEGFR-1-Expressing Endothelial Cells
Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2011-11, Vol.71 (22), p.6976-6985 |
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creator | DAENEN, Laura G. M ROODHART, Jeanine M. L VAN AMERSFOORT, Miranda DEHNAD, Mantre ROESSINGH, Wijnand ULFMAN, Laurien H DERKSEN, Patrick W. B VOEST, Emile E |
description | Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model. This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro. Interestingly, chemotherapy exposure enhanced the expression of VEGF receptor 1 (VEGFR-1) on endothelial cells both in vitro and in vivo. Administration of antibodies targeting VEGFR-1 reversed the early retention of tumor cells in the lungs, thereby preventing the formation of chemotherapy-induced pulmonary metastases. The data indicate that chemotherapy-induced expression of VEGFR-1 on endothelial cells can create an environment favorable to tumor cell homing. Inhibition of VEGFR-1 function may therefore be used to counteract chemotherapy-induced retention of tumor cells within the metastatic niche, providing a novel level of tumor control in chemotherapy. |
doi_str_mv | 10.1158/0008-5472.can-11-0627 |
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M ; ROODHART, Jeanine M. L ; VAN AMERSFOORT, Miranda ; DEHNAD, Mantre ; ROESSINGH, Wijnand ; ULFMAN, Laurien H ; DERKSEN, Patrick W. B ; VOEST, Emile E</creator><creatorcontrib>DAENEN, Laura G. M ; ROODHART, Jeanine M. L ; VAN AMERSFOORT, Miranda ; DEHNAD, Mantre ; ROESSINGH, Wijnand ; ULFMAN, Laurien H ; DERKSEN, Patrick W. B ; VOEST, Emile E</creatorcontrib><description>Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model. This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro. Interestingly, chemotherapy exposure enhanced the expression of VEGF receptor 1 (VEGFR-1) on endothelial cells both in vitro and in vivo. Administration of antibodies targeting VEGFR-1 reversed the early retention of tumor cells in the lungs, thereby preventing the formation of chemotherapy-induced pulmonary metastases. The data indicate that chemotherapy-induced expression of VEGFR-1 on endothelial cells can create an environment favorable to tumor cell homing. Inhibition of VEGFR-1 function may therefore be used to counteract chemotherapy-induced retention of tumor cells within the metastatic niche, providing a novel level of tumor control in chemotherapy.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-11-0627</identifier><identifier>PMID: 21975929</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Cell Adhesion ; Cercopithecus aethiops ; COS Cells ; Endothelial Cells - physiology ; Lung Neoplasms - secondary ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - pathology ; Pharmacology. Drug treatments ; Platelet Endothelial Cell Adhesion Molecule-1 - analysis ; Tumors ; Vascular Endothelial Growth Factor Receptor-1 - analysis ; Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-1 - physiology ; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors</subject><ispartof>Cancer research (Chicago, Ill.), 2011-11, Vol.71 (22), p.6976-6985</ispartof><rights>2015 INIST-CNRS</rights><rights>2011 AACR</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-76f5d5aaf8c621b31af5e6e0c6d6f95b150aca6606bea5be9a84d2b92d6649d83</citedby><cites>FETCH-LOGICAL-c503t-76f5d5aaf8c621b31af5e6e0c6d6f95b150aca6606bea5be9a84d2b92d6649d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25229948$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21975929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DAENEN, Laura G. M</creatorcontrib><creatorcontrib>ROODHART, Jeanine M. L</creatorcontrib><creatorcontrib>VAN AMERSFOORT, Miranda</creatorcontrib><creatorcontrib>DEHNAD, Mantre</creatorcontrib><creatorcontrib>ROESSINGH, Wijnand</creatorcontrib><creatorcontrib>ULFMAN, Laurien H</creatorcontrib><creatorcontrib>DERKSEN, Patrick W. B</creatorcontrib><creatorcontrib>VOEST, Emile E</creatorcontrib><title>Chemotherapy Enhances Metastasis Formation via VEGFR-1-Expressing Endothelial Cells</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model. This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro. Interestingly, chemotherapy exposure enhanced the expression of VEGF receptor 1 (VEGFR-1) on endothelial cells both in vitro and in vivo. Administration of antibodies targeting VEGFR-1 reversed the early retention of tumor cells in the lungs, thereby preventing the formation of chemotherapy-induced pulmonary metastases. The data indicate that chemotherapy-induced expression of VEGFR-1 on endothelial cells can create an environment favorable to tumor cell homing. Inhibition of VEGFR-1 function may therefore be used to counteract chemotherapy-induced retention of tumor cells within the metastatic niche, providing a novel level of tumor control in chemotherapy.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Endothelial Cells - physiology</subject><subject>Lung Neoplasms - secondary</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet Endothelial Cell Adhesion Molecule-1 - analysis</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - analysis</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - physiology</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUhoMobk5_gtIb8SozSZu0uRylm8JU8Os2nKapq_RjJp24f2_K5oRASHje9xwehC4pmVLKk1tCSIJ5FLOphhZTiolg8REaUx4mOI4ifozGB2aEzpz79E9OCT9FI0ZlzCWTY_SSrkzT9StjYb0NsnYFrTYueDA9OH8qF8w720BfdW3wXUHwni3mz5ji7GdtjXNV--FDxVBQV1AHqalrd45OSqidudjfE_Q2z17TO7x8WtynsyXWnIQ9jkXJCw5QJlowmocUSm6EIVoUopQ8p5yABiGIyA3w3EhIooLlkhVCRLJIwgm62fWubfe1Ma5XTeW03wBa022ckiRijMWUepLvSG0756wp1dpWDditokQNOtWgSg2qVDp79F9q0OlzV_sJm7wxxSH1588D13sAnIa6tF5f5f45zpiUURL-Ans9fiw</recordid><startdate>20111115</startdate><enddate>20111115</enddate><creator>DAENEN, Laura G. 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Drug treatments</topic><topic>Platelet Endothelial Cell Adhesion Molecule-1 - analysis</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - analysis</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - physiology</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DAENEN, Laura G. M</creatorcontrib><creatorcontrib>ROODHART, Jeanine M. L</creatorcontrib><creatorcontrib>VAN AMERSFOORT, Miranda</creatorcontrib><creatorcontrib>DEHNAD, Mantre</creatorcontrib><creatorcontrib>ROESSINGH, Wijnand</creatorcontrib><creatorcontrib>ULFMAN, Laurien H</creatorcontrib><creatorcontrib>DERKSEN, Patrick W. 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B</au><au>VOEST, Emile E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemotherapy Enhances Metastasis Formation via VEGFR-1-Expressing Endothelial Cells</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2011-11-15</date><risdate>2011</risdate><volume>71</volume><issue>22</issue><spage>6976</spage><epage>6985</epage><pages>6976-6985</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. 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subjects | Animals Antineoplastic agents Biological and medical sciences Cell Adhesion Cercopithecus aethiops COS Cells Endothelial Cells - physiology Lung Neoplasms - secondary Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology Pharmacology. Drug treatments Platelet Endothelial Cell Adhesion Molecule-1 - analysis Tumors Vascular Endothelial Growth Factor Receptor-1 - analysis Vascular Endothelial Growth Factor Receptor-1 - antagonists & inhibitors Vascular Endothelial Growth Factor Receptor-1 - physiology Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors |
title | Chemotherapy Enhances Metastasis Formation via VEGFR-1-Expressing Endothelial Cells |
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