{"id":2696,"date":"2021-04-28T12:07:44","date_gmt":"2021-04-28T10:07:44","guid":{"rendered":"http:\/\/www.isidorolab.com\/public\/?p=2696"},"modified":"2021-09-05T12:09:46","modified_gmt":"2021-09-05T10:09:46","slug":"cancer-associated-fibroblast-derived-il-6-determines-unfavorable-prognosis-in-cholangiocarcinoma-by-affecting-autophagy-associated-chemoresponse","status":"publish","type":"post","link":"http:\/\/www.isidorolab.com\/public\/index.php\/2021\/04\/28\/cancer-associated-fibroblast-derived-il-6-determines-unfavorable-prognosis-in-cholangiocarcinoma-by-affecting-autophagy-associated-chemoresponse\/","title":{"rendered":"Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"2696\" class=\"elementor elementor-2696\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-6945b8e5 elementor-section-stretched elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"6945b8e5\" data-element_type=\"section\" data-settings=\"{&quot;stretch_section&quot;:&quot;section-stretched&quot;}\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-6873962c\" data-id=\"6873962c\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-cc4d57c elementor-widget elementor-widget-text-editor\" data-id=\"cc4d57c\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Thongchot+S&amp;cauthor_id=33925189\">Suyanee Thongchot<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-2\"> 2 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-3\"> 3 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Vidoni+C&amp;cauthor_id=33925189\">Chiara Vidoni<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ferraresi+A&amp;cauthor_id=33925189\">Alessandra Ferraresi<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Loilome+W&amp;cauthor_id=33925189\">Watcharin Loilome<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-4\"> 4 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Khuntikeo+N&amp;cauthor_id=33925189\">Narong Khuntikeo<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-4\"> 4 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-5\"> 5 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sangkhamanon+S&amp;cauthor_id=33925189\">Sakkarn Sangkhamanon<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-4\"> 4 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-6\"> 6 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Titapun+A&amp;cauthor_id=33925189\">Attapol Titapun<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-4\"> 4 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-5\"> 5 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Isidoro+C&amp;cauthor_id=33925189\">Ciro Isidoro<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-2\"> 2 <\/a><\/sup>,\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Namwat+N&amp;cauthor_id=33925189\">Nisana Namwat<\/a><sup>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-1\"> 1 <\/a>\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33925189\/#affiliation-4\"> 4<\/a><\/sup><\/p>\n\n<h3 class=\"wp-block-heading\">Affiliations<\/h3>\n\n<p><sup>1<\/sup> Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen 40002, Thailand.<\/p>\n<p><sup>2<\/sup> Laboratory of Molecular Pathology, Department of Health Sciences, Universit\u00e0 del Piemonte Orientale &#8220;A. Avogadro&#8221;, Via Solaroli 17, 28100 Novara, Italy.<\/p>\n<p><sup>3<\/sup> Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.<\/p>\n<p><sup>4<\/sup> Cholangiocarcinoma Research Institute, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen 40002, Thailand.<\/p>\n<p><sup>5<\/sup> Department of Surgery, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen 40002, Thailand.<\/p>\n<p><sup>6<\/sup> Department of Pathology, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen 40002, Thailand.<\/p>\n<p>\u00a0<\/p>\n<p><\/p>\n<p>PMID: <strong>33925189<\/strong><\/p>\n<p>PMCID: <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/pmc8124468\/\" target=\"_blank\" rel=\"noreferrer noopener\">PMC8124468<\/a><\/p>\n<p>DOI: <a href=\"https:\/\/doi.org\/10.3390\/cancers13092134\" target=\"_blank\" rel=\"noreferrer noopener\">10.3390\/cancers13092134<\/a><\/p>\n\n<p>Cancers (Basel). 2021 Apr 28;13(9):2134. doi: 10.3390\/cancers13092134.<\/p>\n<p>\u00a0<\/p>\n<hr \/>\n<div id=\"abstract\" class=\"abstract\">\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"enc-abstract\" class=\"abstract-content selected\">\n<p><strong class=\"sub-title\"> Background: <\/strong> Interleukin-6 (IL-6) released by cancer-associated fibroblasts (CAFs) has been shown to associate with the malignant behavior of cholangiocarcinoma (CCA). Here, we aimed to validate with clinical and molecular data the hypothesis that CAF infiltration and release of IL-6 predict poor prognosis in CCA patients following dysregulation of autophagy in cancer cells.<\/p>\n<p><strong class=\"sub-title\"> Methods: <\/strong> Stromal IL-6 and cancer-cell-associated autophagy proteins LC3 and p62 were assayed by Tissue MicroArray immunohistochemistry and their expression correlated with overall survival (OS) in a cohort of 70 CCA patients. The 5-FU cytotoxicity and autophagy were determined in CCA cells cultured with CAF-conditioned medium.<\/p>\n<p><strong class=\"sub-title\"> Results: <\/strong> We show that patients bearing a CCA with low production of stromal IL-6 and active autophagy flux in the cancer cells have the best prognosis and this correlates with a more effective response to post-operative chemotherapy. A similar trend was observed in CCA patients from the TCGA database. In vitro genetic manipulation of IL-6 production by primary CAFs isolated from human CCA showed that IL-6 impairs the autophagy-associated apoptotic response to 5-FU in human CCA cells. Stromal IL-6 inhibition of autophagy in cancer cells was confirmed in an animal model of CCA.<\/p>\n<p><strong class=\"sub-title\"> Conclusion: <\/strong> Our data support a therapeutic strategy that includes autophagy-enhancing drugs along with adjuvants limiting the stromal inflammation (i.e., the secretion of IL-6) to improve the survival of CCA patients.<\/p>\n<\/div>\n<\/div>\n<p>\u00a0<\/p>\n<p>\u00a0<\/p>\n<div id=\"abstract\" class=\"abstract\">\n<p><strong class=\"sub-title\"> Keywords: <\/strong> autophagy; cancer therapy; cancer-associated fibroblasts; cholangiocarcinoma; cytokines; desmoplastic stroma; interleukin-6.<\/p>\n<\/div>\n\n<p>\u00a0<\/p>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t<div style='text-align:center' class='yasr-auto-insert-visitor'><!--Yasr Visitor Votes Shortcode--><div id='yasr_visitor_votes_7ad90de016647' class='yasr-visitor-votes'><div class=\"yasr-custom-text-vv-before yasr-custom-text-vv-before-2696\">Clicca per votare questo articolo!<\/div><div id='yasr-vv-second-row-container-7ad90de016647'\r\n                                        class='yasr-vv-second-row-container'><div id='yasr-visitor-votes-rater-7ad90de016647'\r\n                                      class='yasr-rater-stars-vv'\r\n                                      data-rater-postid='2696'\r\n                                      data-rating='0'\r\n                                      data-rater-starsize='32'\r\n                                      data-rater-readonly='false'\r\n                                      data-rater-nonce='bb8f69d06e'\r\n                                      data-issingular='false'\r\n                                    ><\/div><div class=\"yasr-vv-stats-text-container\" id=\"yasr-vv-stats-text-container-7ad90de016647\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" width=\"20\" height=\"20\"\r\n                                   class=\"yasr-dashicons-visitor-stats\"\r\n                                   data-postid=\"2696\"\r\n                                   id=\"yasr-stats-dashicon-7ad90de016647\">\r\n                                   <path d=\"M18 18v-16h-4v16h4zM12 18v-11h-4v11h4zM6 18v-8h-4v8h4z\"><\/path>\r\n                               <\/svg><span id=\"yasr-vv-text-container-7ad90de016647\" class=\"yasr-vv-text-container\">[Total: <span id=\"yasr-vv-votes-number-container-7ad90de016647\">0<\/span>  Average: <span id=\"yasr-vv-average-container-7ad90de016647\">0<\/span>]<\/span><\/div><div id='yasr-vv-loader-7ad90de016647' class='yasr-vv-container-loader'><\/div><\/div><div id='yasr-vv-bottom-container-7ad90de016647' class='yasr-vv-bottom-container'><\/div><\/div><!--End Yasr Visitor Votes Shortcode--><\/div>","protected":false},"excerpt":{"rendered":"<p>Suyanee Thongchot\u00a0 1 \u00a0 2 \u00a0 3 ,\u00a0Chiara Vidoni\u00a0 2 ,\u00a0Alessandra Ferraresi\u00a0 2 ,\u00a0Watcharin Loilome\u00a0 1 \u00a0 4 ,\u00a0Narong Khuntikeo\u00a0 4 \u00a0 5 ,\u00a0Sakkarn Sangkhamanon\u00a0 4 \u00a0 6 ,\u00a0Attapol Titapun\u00a0 4 \u00a0 5 ,\u00a0Ciro Isidoro\u00a0 2 ,\u00a0Nisana Namwat\u00a0 1 \u00a0 4 Affiliations 1 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway,&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"yasr_overall_rating":0,"yasr_post_is_review":"","yasr_auto_insert_disabled":"","yasr_review_type":"","footnotes":""},"categories":[136],"tags":[44,55],"class_list":["post-2696","post","type-post","status-publish","format-standard","hentry","category-paper","tag-autophagy","tag-cancer"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - 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