IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2
The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysio...
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| creator | Cochaud, Stéphanie Giustiniani, Jérôme Thomas, Clémence Laprevotte, Emilie Garbar, Christian Savoye, Aude-Marie Curé, Hervé Mascaux, Corinne Alberici, Gilles Bonnefoy, Nathalie Eliaou, Jean-François Bensussan, Armand Bastid, Jeremy |
| description | The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(−) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer. |
| doi_str_mv | 10.1038/srep03456 |
| format | Article |
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Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(−) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep03456</identifier><identifier>PMID: 24316750</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/21 ; 13/51 ; 13/95 ; 38/77 ; 631/67/1347 ; 631/67/580 ; Antibodies ; Antineoplastic Agents - pharmacology ; Biopsy ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Chemoresistance ; Chemotherapy ; Drug Resistance, Neoplasm ; Extracellular signal-regulated kinase ; Female ; Humanities and Social Sciences ; Humans ; Inflammation ; Interleukin-17 - biosynthesis ; Interleukin-17 - genetics ; Leukocyte migration ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; MAP kinase ; MAP Kinase Signaling System - drug effects ; Medical prognosis ; Mitogen-Activated Protein Kinase 1 ; Mitogen-Activated Protein Kinase 3 ; multidisciplinary ; Receptors, Estrogen - metabolism ; Science ; Taxoids - pharmacology ; Tumor cell lines ; Tumors</subject><ispartof>Scientific reports, 2013-12, Vol.3 (1), p.3456-3456, Article 3456</ispartof><rights>The Author(s) 2013</rights><rights>Copyright Nature Publishing Group Dec 2013</rights><rights>Copyright © 2013, Macmillan Publishers Limited. All rights reserved 2013 Macmillan Publishers Limited. All rights reserved</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-351edc0c3eaf452e4f9cf69be816a35cb63f9d776b1905a606482c056b15d6a53</citedby><cites>FETCH-LOGICAL-c504t-351edc0c3eaf452e4f9cf69be816a35cb63f9d776b1905a606482c056b15d6a53</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/PMC3856404/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856404/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24316750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cochaud, Stéphanie</creatorcontrib><creatorcontrib>Giustiniani, Jérôme</creatorcontrib><creatorcontrib>Thomas, Clémence</creatorcontrib><creatorcontrib>Laprevotte, Emilie</creatorcontrib><creatorcontrib>Garbar, Christian</creatorcontrib><creatorcontrib>Savoye, Aude-Marie</creatorcontrib><creatorcontrib>Curé, Hervé</creatorcontrib><creatorcontrib>Mascaux, Corinne</creatorcontrib><creatorcontrib>Alberici, Gilles</creatorcontrib><creatorcontrib>Bonnefoy, Nathalie</creatorcontrib><creatorcontrib>Eliaou, Jean-François</creatorcontrib><creatorcontrib>Bensussan, Armand</creatorcontrib><creatorcontrib>Bastid, Jeremy</creatorcontrib><title>IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(−) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.</description><subject>13/1</subject><subject>13/21</subject><subject>13/51</subject><subject>13/95</subject><subject>38/77</subject><subject>631/67/1347</subject><subject>631/67/580</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biopsy</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Drug Resistance, Neoplasm</subject><subject>Extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin-17 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cochaud, Stéphanie</au><au>Giustiniani, Jérôme</au><au>Thomas, Clémence</au><au>Laprevotte, Emilie</au><au>Garbar, Christian</au><au>Savoye, Aude-Marie</au><au>Curé, Hervé</au><au>Mascaux, Corinne</au><au>Alberici, Gilles</au><au>Bonnefoy, Nathalie</au><au>Eliaou, Jean-François</au><au>Bensussan, Armand</au><au>Bastid, Jeremy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2013-12-09</date><risdate>2013</risdate><volume>3</volume><issue>1</issue><spage>3456</spage><epage>3456</epage><pages>3456-3456</pages><artnum>3456</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The proinflammatory cytokine Interleukin 17A (hereafter named IL–17A) or IL-17A producing cells are elevated in breast tumors environment and correlate with poor prognosis. Increased IL-17A is associated with ER(−) or triple negative tumors and reduced Disease Free Survival. However, the pathophysiological role of IL-17A in breast cancer remains unclear although several studies suggested its involvement in cancer cell dissemination. Here we demonstrated that a subset of breast tumors is infiltrated with IL-17A-producing cells. Increased IL-17A seems mainly associated to ER(−) and triple negative/basal-like tumors. Isolation of tumor infiltrating T lymphocytes (TILs) from breast cancer biopsies revealed that these cells secreted significant amounts of IL-17A. We further established that recombinant IL-17A recruits the MAPK pathway by upregulating phosphorylated ERK1/2 in human breast cancer cell lines thereby promoting proliferation and resistance to conventional chemotherapeutic agents such as docetaxel. We also confirmed here that recombinant IL-17A stimulates migration and invasion of breast cancer cells as previously reported. Importantly, TILs also induced tumor cell proliferation, chemoresistance and migration and treatment with IL-17A-neutralizing antibodies abrogated these effects. Altogether these results demonstrated the pathophysiological role of IL-17A-producing cell infiltrate in a subset of breast cancers. Therefore, IL-17A appears as potential therapeutic target for breast cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24316750</pmid><doi>10.1038/srep03456</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/1 13/21 13/51 13/95 38/77 631/67/1347 631/67/580 Antibodies Antineoplastic Agents - pharmacology Biopsy Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Chemoresistance Chemotherapy Drug Resistance, Neoplasm Extracellular signal-regulated kinase Female Humanities and Social Sciences Humans Inflammation Interleukin-17 - biosynthesis Interleukin-17 - genetics Leukocyte migration Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism MAP kinase MAP Kinase Signaling System - drug effects Medical prognosis Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 multidisciplinary Receptors, Estrogen - metabolism Science Taxoids - pharmacology Tumor cell lines Tumors |
| title | IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2 |
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