Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment
ObjectivesThe tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC),...
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| Veröffentlicht in: | Gut 2015-12, Vol.64 (12), p.1921-1935 |
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| creator | Sainz, Bruno Alcala, Sonia Garcia, Elena Sanchez-Ripoll, Yolanda Azevedo, Maria M Cioffi, Michele Tatari, Marianthi Miranda-Lorenzo, Irene Hidalgo, Manuel Gomez-Lopez, Gonzalo Cañamero, Marta Erkan, Mert Kleeff, Jörg García-Silva, Susana Sancho, Patricia Hermann, Patrick C Heeschen, Christopher |
| description | ObjectivesThe tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance.DesignMicroarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology.ResultsWe found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R.ConclusionsThus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis. |
| doi_str_mv | 10.1136/gutjnl-2014-308935 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808671424</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4014748121</sourcerecordid><originalsourceid>FETCH-LOGICAL-b446t-f634f0cd17da224a9772f6ec299cb2784f92a66ffed853bb78495e2ae9f468d23</originalsourceid><addsrcrecordid>eNqNkU1vFSEUhomxsdfqH3BhSNy4wfI1Ayybm_qRXNMudE0YBurcDHAFpsn992Uy1YUrVyTkeV8O5wHgHcGfCGH99cNSj3FGFBOOGJaKdS_AjvBeIkalfAl2GBOBOsHVJXhdyhFjLKUir8Al7SQnlMkdOH-fbE4uPk45xeBiNTP8tb-5R0ReHw6ICXjKKaTqCjyZaLMzdbJwXOwKmtHFZE22U0zBwOEMja3TY0PiA5xqgbZFXIalugCtm2doUziZXNeH3oALb-bi3j6fV-Dn59sf-6_ocPfl2_7mgAbO-4p8z7jHdiRiNJRyo4SgvneWKmUHKiT3ipq-996NsmPD0G5U56hxyrdNjJRdgY9bb_vI78WVqsNU1mFMdGkpmkgse0E45Q398A96TEuObTpNhFBcUCW6RtGNaosrJTuvT3kKJp81wXoVozcxehWjNzEt9P65ehmCG_9G_phoANqAIRz_p_AJgf2aBQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779472975</pqid></control><display><type>article</type><title>Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><source>PubMed Central</source><creator>Sainz, Bruno ; Alcala, Sonia ; Garcia, Elena ; Sanchez-Ripoll, Yolanda ; Azevedo, Maria M ; Cioffi, Michele ; Tatari, Marianthi ; Miranda-Lorenzo, Irene ; Hidalgo, Manuel ; Gomez-Lopez, Gonzalo ; Cañamero, Marta ; Erkan, Mert ; Kleeff, Jörg ; García-Silva, Susana ; Sancho, Patricia ; Hermann, Patrick C ; Heeschen, Christopher</creator><creatorcontrib>Sainz, Bruno ; Alcala, Sonia ; Garcia, Elena ; Sanchez-Ripoll, Yolanda ; Azevedo, Maria M ; Cioffi, Michele ; Tatari, Marianthi ; Miranda-Lorenzo, Irene ; Hidalgo, Manuel ; Gomez-Lopez, Gonzalo ; Cañamero, Marta ; Erkan, Mert ; Kleeff, Jörg ; García-Silva, Susana ; Sancho, Patricia ; Hermann, Patrick C ; Heeschen, Christopher</creatorcontrib><description>ObjectivesThe tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance.DesignMicroarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology.ResultsWe found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R.ConclusionsThus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2014-308935</identifier><identifier>PMID: 25841238</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Activins - metabolism ; Animals ; Antimicrobial Cationic Peptides - metabolism ; Antimicrobial Cationic Peptides - pharmacology ; Cancer therapies ; Carcinogenesis - drug effects ; Carcinogenesis - genetics ; Carcinogenesis - metabolism ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - pathology ; Cell Self Renewal - drug effects ; Gene Expression - drug effects ; Growth factors ; Humans ; Kinases ; Macrophages - drug effects ; Macrophages - metabolism ; Metastasis ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Ovarian cancer ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Peptides ; Protein Array Analysis ; Proteins ; Purinergic P2X Receptor Antagonists - pharmacology ; Receptors, Formyl Peptide - antagonists & inhibitors ; Receptors, Formyl Peptide - metabolism ; Receptors, Purinergic P2X7 - metabolism ; Signal Transduction - drug effects ; Stem cells ; Studies ; Tissue Array Analysis ; Transforming Growth Factor beta1 - pharmacology ; Tumor Microenvironment ; Tumors</subject><ispartof>Gut, 2015-12, Vol.64 (12), p.1921-1935</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing</rights><rights>Copyright: 2015 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b446t-f634f0cd17da224a9772f6ec299cb2784f92a66ffed853bb78495e2ae9f468d23</citedby><cites>FETCH-LOGICAL-b446t-f634f0cd17da224a9772f6ec299cb2784f92a66ffed853bb78495e2ae9f468d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://gut.bmj.com/content/64/12/1921.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://gut.bmj.com/content/64/12/1921.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77569,77600</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25841238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sainz, Bruno</creatorcontrib><creatorcontrib>Alcala, Sonia</creatorcontrib><creatorcontrib>Garcia, Elena</creatorcontrib><creatorcontrib>Sanchez-Ripoll, Yolanda</creatorcontrib><creatorcontrib>Azevedo, Maria M</creatorcontrib><creatorcontrib>Cioffi, Michele</creatorcontrib><creatorcontrib>Tatari, Marianthi</creatorcontrib><creatorcontrib>Miranda-Lorenzo, Irene</creatorcontrib><creatorcontrib>Hidalgo, Manuel</creatorcontrib><creatorcontrib>Gomez-Lopez, Gonzalo</creatorcontrib><creatorcontrib>Cañamero, Marta</creatorcontrib><creatorcontrib>Erkan, Mert</creatorcontrib><creatorcontrib>Kleeff, Jörg</creatorcontrib><creatorcontrib>García-Silva, Susana</creatorcontrib><creatorcontrib>Sancho, Patricia</creatorcontrib><creatorcontrib>Hermann, Patrick C</creatorcontrib><creatorcontrib>Heeschen, Christopher</creatorcontrib><title>Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment</title><title>Gut</title><addtitle>Gut</addtitle><description>ObjectivesThe tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance.DesignMicroarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology.ResultsWe found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R.ConclusionsThus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.</description><subject>Activins - metabolism</subject><subject>Animals</subject><subject>Antimicrobial Cationic Peptides - metabolism</subject><subject>Antimicrobial Cationic Peptides - pharmacology</subject><subject>Cancer therapies</subject><subject>Carcinogenesis - drug effects</subject><subject>Carcinogenesis - genetics</subject><subject>Carcinogenesis - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Cell Self Renewal - drug effects</subject><subject>Gene Expression - drug effects</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Kinases</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Ovarian cancer</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Peptides</subject><subject>Protein Array Analysis</subject><subject>Proteins</subject><subject>Purinergic P2X Receptor Antagonists - pharmacology</subject><subject>Receptors, Formyl Peptide - antagonists & inhibitors</subject><subject>Receptors, Formyl Peptide - metabolism</subject><subject>Receptors, Purinergic P2X7 - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Tissue Array Analysis</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Tumor 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hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment</title><author>Sainz, Bruno ; Alcala, Sonia ; Garcia, Elena ; Sanchez-Ripoll, Yolanda ; Azevedo, Maria M ; Cioffi, Michele ; Tatari, Marianthi ; Miranda-Lorenzo, Irene ; Hidalgo, Manuel ; Gomez-Lopez, Gonzalo ; Cañamero, Marta ; Erkan, Mert ; Kleeff, Jörg ; García-Silva, Susana ; Sancho, Patricia ; Hermann, Patrick C ; Heeschen, Christopher</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b446t-f634f0cd17da224a9772f6ec299cb2784f92a66ffed853bb78495e2ae9f468d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Activins - metabolism</topic><topic>Animals</topic><topic>Antimicrobial Cationic Peptides - metabolism</topic><topic>Antimicrobial Cationic Peptides - pharmacology</topic><topic>Cancer therapies</topic><topic>Carcinogenesis - drug effects</topic><topic>Carcinogenesis - genetics</topic><topic>Carcinogenesis - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Cell Self Renewal - drug effects</topic><topic>Gene Expression - drug effects</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Kinases</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Ovarian cancer</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Peptides</topic><topic>Protein Array Analysis</topic><topic>Proteins</topic><topic>Purinergic P2X Receptor Antagonists - pharmacology</topic><topic>Receptors, Formyl Peptide - antagonists & inhibitors</topic><topic>Receptors, Formyl Peptide - metabolism</topic><topic>Receptors, Purinergic P2X7 - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Tissue Array Analysis</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sainz, Bruno</creatorcontrib><creatorcontrib>Alcala, Sonia</creatorcontrib><creatorcontrib>Garcia, Elena</creatorcontrib><creatorcontrib>Sanchez-Ripoll, Yolanda</creatorcontrib><creatorcontrib>Azevedo, Maria M</creatorcontrib><creatorcontrib>Cioffi, Michele</creatorcontrib><creatorcontrib>Tatari, Marianthi</creatorcontrib><creatorcontrib>Miranda-Lorenzo, Irene</creatorcontrib><creatorcontrib>Hidalgo, Manuel</creatorcontrib><creatorcontrib>Gomez-Lopez, Gonzalo</creatorcontrib><creatorcontrib>Cañamero, Marta</creatorcontrib><creatorcontrib>Erkan, Mert</creatorcontrib><creatorcontrib>Kleeff, Jörg</creatorcontrib><creatorcontrib>García-Silva, Susana</creatorcontrib><creatorcontrib>Sancho, Patricia</creatorcontrib><creatorcontrib>Hermann, Patrick C</creatorcontrib><creatorcontrib>Heeschen, Christopher</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest 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Abstracts</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sainz, Bruno</au><au>Alcala, Sonia</au><au>Garcia, Elena</au><au>Sanchez-Ripoll, Yolanda</au><au>Azevedo, Maria M</au><au>Cioffi, Michele</au><au>Tatari, Marianthi</au><au>Miranda-Lorenzo, Irene</au><au>Hidalgo, Manuel</au><au>Gomez-Lopez, Gonzalo</au><au>Cañamero, Marta</au><au>Erkan, Mert</au><au>Kleeff, Jörg</au><au>García-Silva, Susana</au><au>Sancho, Patricia</au><au>Hermann, Patrick C</au><au>Heeschen, Christopher</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment</atitle><jtitle>Gut</jtitle><addtitle>Gut</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>64</volume><issue>12</issue><spage>1921</spage><epage>1935</epage><pages>1921-1935</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>ObjectivesThe tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance.DesignMicroarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology.ResultsWe found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R.ConclusionsThus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>25841238</pmid><doi>10.1136/gutjnl-2014-308935</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_proquest_miscellaneous_1808671424 |
| source | MEDLINE; BMJ Journals - NESLi2; PubMed Central |
| subjects | Activins - metabolism Animals Antimicrobial Cationic Peptides - metabolism Antimicrobial Cationic Peptides - pharmacology Cancer therapies Carcinogenesis - drug effects Carcinogenesis - genetics Carcinogenesis - metabolism Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Cell Self Renewal - drug effects Gene Expression - drug effects Growth factors Humans Kinases Macrophages - drug effects Macrophages - metabolism Metastasis Mice Mice, Nude Neoplasm Invasiveness Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Ovarian cancer Pancreatic cancer Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Peptides Protein Array Analysis Proteins Purinergic P2X Receptor Antagonists - pharmacology Receptors, Formyl Peptide - antagonists & inhibitors Receptors, Formyl Peptide - metabolism Receptors, Purinergic P2X7 - metabolism Signal Transduction - drug effects Stem cells Studies Tissue Array Analysis Transforming Growth Factor beta1 - pharmacology Tumor Microenvironment Tumors |
| title | Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T09%3A31%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Microenvironmental%20hCAP-18/LL-37%20promotes%20pancreatic%20ductal%20adenocarcinoma%20by%20activating%20its%20cancer%20stem%20cell%20compartment&rft.jtitle=Gut&rft.au=Sainz,%20Bruno&rft.date=2015-12-01&rft.volume=64&rft.issue=12&rft.spage=1921&rft.epage=1935&rft.pages=1921-1935&rft.issn=0017-5749&rft.eissn=1468-3288&rft.coden=GUTTAK&rft_id=info:doi/10.1136/gutjnl-2014-308935&rft_dat=%3Cproquest_cross%3E4014748121%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1779472975&rft_id=info:pmid/25841238&rfr_iscdi=true |