The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells
The present study demonstrates that hypoxia activates a novel T cell‐mediated mechanism of neovascularization triggered by VEGF in which p66Shc acts as the master regulator. Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic...
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| Veröffentlicht in: | Journal of leukocyte biology 2010-03, Vol.87 (3), p.365-369 |
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| container_title | Journal of leukocyte biology |
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| creator | Naldini, Antonella Morena, Emilia Pucci, Annalisa Pellegrini, Michela Baldari, Cosima T. Pelicci, Pier Giuseppe Presta, Marco Ribatti, Domenico Carraro, Fabio |
| description | The present study demonstrates that hypoxia activates a novel T cell‐mediated mechanism of neovascularization triggered by VEGF in which p66Shc acts as the master regulator.
Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti‐VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up‐regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc−/− mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc−/− splenocytes was reduced dramatically when compared with the wild‐type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF‐mediated mechanism, where p66Shc acts as a positive regulator. |
| doi_str_mv | 10.1189/jlb.0709460 |
| format | Article |
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Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti‐VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up‐regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc−/− mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc−/− splenocytes was reduced dramatically when compared with the wild‐type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF‐mediated mechanism, where p66Shc acts as a positive regulator.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.0709460</identifier><identifier>PMID: 19889727</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Animals ; Cell Hypoxia ; Chick Embryo ; cytokines ; Gene Deletion ; Gene Expression Regulation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; inflammation ; Jurkat Cells ; Leukocytes, Mononuclear - metabolism ; Mice ; Neovascularization, Physiologic ; Shc Signaling Adaptor Proteins - metabolism ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; T lymphocytes ; T-Lymphocytes - cytology ; T-Lymphocytes - metabolism ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Journal of leukocyte biology, 2010-03, Vol.87 (3), p.365-369</ispartof><rights>2010 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3965-5d6f2b2b85eab2ef8deac1c5021029976f03b72820757134adf4d930fb59c9a43</citedby><cites>FETCH-LOGICAL-c3965-5d6f2b2b85eab2ef8deac1c5021029976f03b72820757134adf4d930fb59c9a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.0709460$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.0709460$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19889727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naldini, Antonella</creatorcontrib><creatorcontrib>Morena, Emilia</creatorcontrib><creatorcontrib>Pucci, Annalisa</creatorcontrib><creatorcontrib>Pellegrini, Michela</creatorcontrib><creatorcontrib>Baldari, Cosima T.</creatorcontrib><creatorcontrib>Pelicci, Pier Giuseppe</creatorcontrib><creatorcontrib>Presta, Marco</creatorcontrib><creatorcontrib>Ribatti, Domenico</creatorcontrib><creatorcontrib>Carraro, Fabio</creatorcontrib><title>The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>The present study demonstrates that hypoxia activates a novel T cell‐mediated mechanism of neovascularization triggered by VEGF in which p66Shc acts as the master regulator.
Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti‐VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up‐regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc−/− mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc−/− splenocytes was reduced dramatically when compared with the wild‐type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF‐mediated mechanism, where p66Shc acts as a positive regulator.</description><subject>Animals</subject><subject>Cell Hypoxia</subject><subject>Chick Embryo</subject><subject>cytokines</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>inflammation</subject><subject>Jurkat Cells</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Mice</subject><subject>Neovascularization, Physiologic</subject><subject>Shc Signaling Adaptor Proteins - metabolism</subject><subject>Src Homology 2 Domain-Containing, Transforming Protein 1</subject><subject>T lymphocytes</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kL1v2zAQxYkiQeOmnboHXIIMhZwjKZHi2AT9SGAgizsTFHWyaMiSIkpV_N-Hgg1063TD-713d4-QrwzWjOX6ft8Ua1CgUwkfyIppkSdCKnFBVqBSlmQpwBX5FMIeAASX8JFcMZ3nWnG1IvW2RmpL24_dQPuhG9G3tJcy1I76QC3tu-BH_xfpgLupsQsWiXFxtTvf7bD1Lmqh79qAUSonhyUtjrQ-9t1b1LbUYdOEz-Sysk3AL-d5Tf78_LF9_J1sXn49PX7fJE5omSVZKSte8CLP0BYcq7xE65jLgDPgWitZgSgUzzmoTDGR2rJKSy2gKjLttE3FNbk75cZnXicMozn4sFxgW-ymYJQQUstUQyS_nUg3dCEMWJl-8Ac7HA0DszRrYrPm3Gykb865U3HA8h97rjICcAJm3-Dxf1nmefMAQmbRcnuy1H5Xz35AEw62aeIGbuZ5zpURZuHeAUwRkG0</recordid><startdate>201003</startdate><enddate>201003</enddate><creator>Naldini, Antonella</creator><creator>Morena, Emilia</creator><creator>Pucci, Annalisa</creator><creator>Pellegrini, Michela</creator><creator>Baldari, Cosima T.</creator><creator>Pelicci, Pier Giuseppe</creator><creator>Presta, Marco</creator><creator>Ribatti, Domenico</creator><creator>Carraro, Fabio</creator><general>Society for Leukocyte Biology</general><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></search><sort><creationdate>201003</creationdate><title>The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells</title><author>Naldini, Antonella ; Morena, Emilia ; Pucci, Annalisa ; Pellegrini, Michela ; Baldari, Cosima T. ; Pelicci, Pier Giuseppe ; Presta, Marco ; Ribatti, Domenico ; Carraro, Fabio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3965-5d6f2b2b85eab2ef8deac1c5021029976f03b72820757134adf4d930fb59c9a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Cell Hypoxia</topic><topic>Chick Embryo</topic><topic>cytokines</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>inflammation</topic><topic>Jurkat Cells</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Mice</topic><topic>Neovascularization, Physiologic</topic><topic>Shc Signaling Adaptor Proteins - metabolism</topic><topic>Src Homology 2 Domain-Containing, Transforming Protein 1</topic><topic>T lymphocytes</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naldini, Antonella</creatorcontrib><creatorcontrib>Morena, Emilia</creatorcontrib><creatorcontrib>Pucci, Annalisa</creatorcontrib><creatorcontrib>Pellegrini, Michela</creatorcontrib><creatorcontrib>Baldari, Cosima T.</creatorcontrib><creatorcontrib>Pelicci, Pier Giuseppe</creatorcontrib><creatorcontrib>Presta, Marco</creatorcontrib><creatorcontrib>Ribatti, Domenico</creatorcontrib><creatorcontrib>Carraro, Fabio</creatorcontrib><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><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naldini, Antonella</au><au>Morena, Emilia</au><au>Pucci, Annalisa</au><au>Pellegrini, Michela</au><au>Baldari, Cosima T.</au><au>Pelicci, Pier Giuseppe</au><au>Presta, Marco</au><au>Ribatti, Domenico</au><au>Carraro, Fabio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2010-03</date><risdate>2010</risdate><volume>87</volume><issue>3</issue><spage>365</spage><epage>369</epage><pages>365-369</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>The present study demonstrates that hypoxia activates a novel T cell‐mediated mechanism of neovascularization triggered by VEGF in which p66Shc acts as the master regulator.
Immune cells play an important role in the onset of angiogenesis. Here, we report that VEGF represents the major proangiogenic factor expressed by T cells exposed to hypoxia, a common feature of inflammation and tumor microenvironment. The supernatants of hypoxic T cells were highly angiogenic when delivered on the chick embryo CAM. The angiogenic response was abrogated by a neutralizing anti‐VEGF antibody and mimicked by rVEGF. Interestingly, VEGF induction by hypoxia was up‐regulated in Jurkat T cells overexpressing the adaptor protein p66Shc but not the inactive S36 p66Shc mutant, and it was abolished in p66Shc−/− mouse splenocytes. Accordingly, the angiogenic response induced by the supernatants from hypoxic p66Shc−/− splenocytes was reduced dramatically when compared with the wild‐type controls. In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF‐mediated mechanism, where p66Shc acts as a positive regulator.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>19889727</pmid><doi>10.1189/jlb.0709460</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Animals Cell Hypoxia Chick Embryo cytokines Gene Deletion Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit - metabolism inflammation Jurkat Cells Leukocytes, Mononuclear - metabolism Mice Neovascularization, Physiologic Shc Signaling Adaptor Proteins - metabolism Src Homology 2 Domain-Containing, Transforming Protein 1 T lymphocytes T-Lymphocytes - cytology T-Lymphocytes - metabolism Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
| title | The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells |
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