Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages
Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelia...
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| Veröffentlicht in: | The Journal of experimental medicine 2008-07, Vol.205 (7), p.1673-1685 |
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| creator | Sierra, Jose Rafael Corso, Simona Caione, Luisa Cepero, Virna Conrotto, Paolo Cignetti, Alessandro Piacibello, Wanda Kumanogoh, Atsushi Kikutani, Hitoshi Comoglio, Paolo Maria Tamagnone, Luca Giordano, Silvia |
| description | Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321-4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target. |
| doi_str_mv | 10.1084/jem.20072602 |
| format | Article |
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We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321-4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>EISSN: 1892-1007</identifier><identifier>DOI: 10.1084/jem.20072602</identifier><identifier>PMID: 18559453</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Angiogenesis Inducing Agents - metabolism ; Animals ; Cell Line ; Humans ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - pathology ; Macrophages - metabolism ; Macrophages - pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Neoplasm Metastasis ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Semaphorins - genetics ; Semaphorins - metabolism</subject><ispartof>The Journal of experimental medicine, 2008-07, Vol.205 (7), p.1673-1685</ispartof><rights>2008 Sierra et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-203d098c32d9e17975996390c14d55d51129bcc1b5d5358185fdc78d725e02513</citedby><cites>FETCH-LOGICAL-c479t-203d098c32d9e17975996390c14d55d51129bcc1b5d5358185fdc78d725e02513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18559453$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sierra, Jose Rafael</creatorcontrib><creatorcontrib>Corso, Simona</creatorcontrib><creatorcontrib>Caione, Luisa</creatorcontrib><creatorcontrib>Cepero, Virna</creatorcontrib><creatorcontrib>Conrotto, Paolo</creatorcontrib><creatorcontrib>Cignetti, Alessandro</creatorcontrib><creatorcontrib>Piacibello, Wanda</creatorcontrib><creatorcontrib>Kumanogoh, Atsushi</creatorcontrib><creatorcontrib>Kikutani, Hitoshi</creatorcontrib><creatorcontrib>Comoglio, Paolo Maria</creatorcontrib><creatorcontrib>Tamagnone, Luca</creatorcontrib><creatorcontrib>Giordano, Silvia</creatorcontrib><title>Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321-4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. 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Corso, Simona ; Caione, Luisa ; Cepero, Virna ; Conrotto, Paolo ; Cignetti, Alessandro ; Piacibello, Wanda ; Kumanogoh, Atsushi ; Kikutani, Hitoshi ; Comoglio, Paolo Maria ; Tamagnone, Luca ; Giordano, Silvia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-203d098c32d9e17975996390c14d55d51129bcc1b5d5358185fdc78d725e02513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Angiogenesis Inducing Agents - metabolism</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Humans</topic><topic>Inflammation - genetics</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Semaphorins - genetics</topic><topic>Semaphorins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sierra, Jose Rafael</creatorcontrib><creatorcontrib>Corso, Simona</creatorcontrib><creatorcontrib>Caione, Luisa</creatorcontrib><creatorcontrib>Cepero, Virna</creatorcontrib><creatorcontrib>Conrotto, Paolo</creatorcontrib><creatorcontrib>Cignetti, Alessandro</creatorcontrib><creatorcontrib>Piacibello, Wanda</creatorcontrib><creatorcontrib>Kumanogoh, Atsushi</creatorcontrib><creatorcontrib>Kikutani, Hitoshi</creatorcontrib><creatorcontrib>Comoglio, Paolo Maria</creatorcontrib><creatorcontrib>Tamagnone, Luca</creatorcontrib><creatorcontrib>Giordano, Silvia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sierra, Jose Rafael</au><au>Corso, Simona</au><au>Caione, Luisa</au><au>Cepero, Virna</au><au>Conrotto, Paolo</au><au>Cignetti, Alessandro</au><au>Piacibello, Wanda</au><au>Kumanogoh, Atsushi</au><au>Kikutani, Hitoshi</au><au>Comoglio, Paolo Maria</au><au>Tamagnone, Luca</au><au>Giordano, Silvia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2008-07-07</date><risdate>2008</risdate><volume>205</volume><issue>7</issue><spage>1673</spage><epage>1685</epage><pages>1673-1685</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><eissn>1892-1007</eissn><abstract>Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Angiogenesis Inducing Agents - metabolism Animals Cell Line Humans Inflammation - genetics Inflammation - metabolism Inflammation - pathology Macrophages - metabolism Macrophages - pathology Mice Mice, Inbred BALB C Mice, Knockout Neoplasm Metastasis Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Neovascularization, Pathologic - genetics Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Semaphorins - genetics Semaphorins - metabolism |
| title | Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages |
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