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Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth
Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in...
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| Published in: | Cancer research (Chicago, Ill.) Ill.), 2010-10, Vol.70 (20), p.8211-8221 |
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| cites | cdi_FETCH-LOGICAL-c483t-eeb8cb3a734a6ffdb3e3023a0fa78d02bd21b8a731ddd69deb2e6a2fb2c0bf13 |
| container_end_page | 8221 |
| container_issue | 20 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | MURAMATSU, Masashi YAMAMOTO, Seiji OSAWA, Tsuyoshi SHIBUYA, Masabumi |
| description | Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression. |
| doi_str_mv | 10.1158/0008-5472.can-10-0202 |
| format | article |
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Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-10-0202</identifier><identifier>PMID: 20924106</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Alternative Splicing ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Bone Marrow Cells - pathology ; Bone Marrow Cells - physiology ; Carcinoma, Lewis Lung - pathology ; Cell Division ; Cell Line, Tumor ; DNA Primers ; Female ; Fibroblast Growth Factor 2 - genetics ; Lung Neoplasms - pathology ; Macrophages - pathology ; Macrophages - physiology ; Medical sciences ; Mice ; Mice, Knockout ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasms - pathology ; Neovascularization, Pathologic - pathology ; Pharmacology. Drug treatments ; Receptor, Fibroblast Growth Factor, Type 1 - deficiency ; Receptor, Fibroblast Growth Factor, Type 1 - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tumors ; Uterine Neoplasms - pathology ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor Receptor-1 - physiology</subject><ispartof>Cancer research (Chicago, Ill.), 2010-10, Vol.70 (20), p.8211-8221</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-eeb8cb3a734a6ffdb3e3023a0fa78d02bd21b8a731ddd69deb2e6a2fb2c0bf13</citedby><cites>FETCH-LOGICAL-c483t-eeb8cb3a734a6ffdb3e3023a0fa78d02bd21b8a731ddd69deb2e6a2fb2c0bf13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23324897$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20924106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MURAMATSU, Masashi</creatorcontrib><creatorcontrib>YAMAMOTO, Seiji</creatorcontrib><creatorcontrib>OSAWA, Tsuyoshi</creatorcontrib><creatorcontrib>SHIBUYA, Masabumi</creatorcontrib><title>Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression.</description><subject>Alternative Splicing</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - pathology</subject><subject>Bone Marrow Cells - physiology</subject><subject>Carcinoma, Lewis Lung - pathology</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>DNA Primers</subject><subject>Female</subject><subject>Fibroblast Growth Factor 2 - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Macrophages - pathology</subject><subject>Macrophages - physiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Multiple tumors. Solid tumors. 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Drug treatments</subject><subject>Receptor, Fibroblast Growth Factor, Type 1 - deficiency</subject><subject>Receptor, Fibroblast Growth Factor, Type 1 - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumors</subject><subject>Uterine Neoplasms - pathology</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - physiology</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkc1uEzEUhS0EoqHwCCBvEKsp_pmJnWWJ2oKUAiIR29H1X2LksYM9IwTPwsPiUUJZsrr29XfuufJB6CUlV5R28i0hRDZdK9iVhthQ0hBG2CO0oB2XjWjb7jFaPDAX6Fkp3-q1o6R7ii4YWbGWkuUC_f4KRU8BMr6JJo0HGzwEfJfTj_GAb0GPKeMvVttjPTQUb_0-QvBxjz_nNKTRFnyflA_-F4w-RZwcvged0_EAe4s3Ptq5rm0IBbuqwO9StBXJ1QBDNHg7-qHaz4O2KXiDd9NQLU8LPEdPHIRiX5zrJdrd3uzW75vNp7sP6-tNo1vJx8ZaJbXiIHgLS-eM4pYTxoE4ENIQpgyjStZnaoxZroxVzC6BOcU0UY7yS_TmNPaY0_fJlrEffNF1Z4g2TaWXoqVCLoX4Lyk6KbmQfFXJ7kTWzyglW9cfsx8g_-wp6ecA-zmcfg6nX19_nLtzgFX36uwwqcGaB9XfxCrw-gzU4CC4DFH78o_jnLVyJfgflsundg</recordid><startdate>20101015</startdate><enddate>20101015</enddate><creator>MURAMATSU, Masashi</creator><creator>YAMAMOTO, Seiji</creator><creator>OSAWA, Tsuyoshi</creator><creator>SHIBUYA, Masabumi</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20101015</creationdate><title>Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth</title><author>MURAMATSU, Masashi ; YAMAMOTO, Seiji ; OSAWA, Tsuyoshi ; SHIBUYA, Masabumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-eeb8cb3a734a6ffdb3e3023a0fa78d02bd21b8a731ddd69deb2e6a2fb2c0bf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Alternative Splicing</topic><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - pathology</topic><topic>Bone Marrow Cells - physiology</topic><topic>Carcinoma, Lewis Lung - pathology</topic><topic>Cell Division</topic><topic>Cell Line, Tumor</topic><topic>DNA Primers</topic><topic>Female</topic><topic>Fibroblast Growth Factor 2 - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Macrophages - pathology</topic><topic>Macrophages - physiology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasms - pathology</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptor, Fibroblast Growth Factor, Type 1 - deficiency</topic><topic>Receptor, Fibroblast Growth Factor, Type 1 - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tumors</topic><topic>Uterine Neoplasms - pathology</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MURAMATSU, Masashi</creatorcontrib><creatorcontrib>YAMAMOTO, Seiji</creatorcontrib><creatorcontrib>OSAWA, Tsuyoshi</creatorcontrib><creatorcontrib>SHIBUYA, Masabumi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MURAMATSU, Masashi</au><au>YAMAMOTO, Seiji</au><au>OSAWA, Tsuyoshi</au><au>SHIBUYA, Masabumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2010-10-15</date><risdate>2010</risdate><volume>70</volume><issue>20</issue><spage>8211</spage><epage>8221</epage><pages>8211-8221</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>ObjectType-Article-2</notes><notes>ObjectType-Feature-1</notes><abstract>Vascular endothelial growth factor and its receptors, including Flt-1 and Flk-1, are involved in angiogenesis under physiologic and pathologic conditions. Recently, Flt-1-expressing cells were reported to contribute to the intracranial growth of glioma cells. However, the role of Flt-1 signaling in solid tumor growth in s.c. tissue has not been elucidated. To investigate how Flt-1 signaling is involved in the proliferation of solid tumors, we implanted tumor cells into wild-type (Wt) and Flt-1 tyrosine kinase (TK)-deficient (Flt-1 TK(-/-)) mice. Growth of HSML and B16 but not Lewis lung carcinoma cell in s.c. tissue was significantly decreased in Flt-1 TK(-/-) mice. Angiogenesis in HSML and B16 tumors was remarkably reduced in Flt-1 TK(-/-) mice. Moreover, the infiltration of macrophage lineage cells into HSML and B16 tumors was clearly suppressed in Flt-1 TK(-/-) mice. Pericyte marker(+) cells were also reduced in Flt-1 TK(-/-) mice. However, in the border area of tumor, angiogenesis and the infiltration of macrophage lineage cell were basically similar between Wt and Flt-1 TK(-/-) mice. In bone marrow (BM) transplantation experiments, tumor angiogenesis, infiltration of macrophage lineage cells, and tumor growth were significantly suppressed in Wt/Flt-1 TK(-/-) mice implanted with Flt-1 TK(-/-) BM cells compared with those implanted with Wt BM cells. We conclude that Flt-1 signaling is involved in the function of BM-derived cell, such as the migration of macrophages into cancerous tissues, and significantly contributes to angiogenesis and tumor progression.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>20924106</pmid><doi>10.1158/0008-5472.can-10-0202</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alternative Splicing Animals Antineoplastic agents Biological and medical sciences Bone Marrow Cells - pathology Bone Marrow Cells - physiology Carcinoma, Lewis Lung - pathology Cell Division Cell Line, Tumor DNA Primers Female Fibroblast Growth Factor 2 - genetics Lung Neoplasms - pathology Macrophages - pathology Macrophages - physiology Medical sciences Mice Mice, Knockout Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasms - pathology Neovascularization, Pathologic - pathology Pharmacology. Drug treatments Receptor, Fibroblast Growth Factor, Type 1 - deficiency Receptor, Fibroblast Growth Factor, Type 1 - genetics Reverse Transcriptase Polymerase Chain Reaction Tumors Uterine Neoplasms - pathology Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor Receptor-1 - physiology |
| title | Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Mobilization of Macrophage Lineage Cells from Bone Marrow and Stimulates Solid Tumor Growth |
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