{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:27:12Z","timestamp":1774330032703,"version":"3.50.1"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T00:00:00Z","timestamp":1470873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0160891","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T13:42:02Z","timestamp":1470922922000},"page":"e0160891","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Intricate Macrophage-Colorectal Cancer Cell Communication in Response to Radiation"],"prefix":"10.1371","volume":"11","author":[{"given":"Ana T.","family":"Pinto","sequence":"first","affiliation":[]},{"given":"Marta L.","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"S\u00e9rgia","family":"Velho","sequence":"additional","affiliation":[]},{"given":"Marta T.","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Ana P.","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Figueira","sequence":"additional","affiliation":[]},{"given":"Armanda","family":"Monteiro","sequence":"additional","affiliation":[]},{"given":"Margarida","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Raquel","family":"Seruca","sequence":"additional","affiliation":[]},{"given":"M\u00e1rio A.","family":"Barbosa","sequence":"additional","affiliation":[]},{"given":"Marc","family":"Mareel","sequence":"additional","affiliation":[]},{"given":"Maria J.","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"S\u00f3nia","family":"Rocha","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2016,8,11]]},"reference":[{"issue":"3","key":"ref1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: functions of cells recruited to the tumor microenvironment","volume":"21","author":"D Hanahan","year":"2012","journal-title":"Cancer cell"},{"issue":"4","key":"ref2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc2618","article-title":"Microenvironmental regulation of metastasis","volume":"9","author":"JA Joyce","year":"2009","journal-title":"Nature reviews Cancer"},{"issue":"2","key":"ref3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cell.2006.01.007","article-title":"Macrophages: obligate partners for tumor cell migration, invasion, and metastasis","volume":"124","author":"J Condeelis","year":"2006","journal-title":"Cell"},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrc1256","article-title":"Tumour-educated macrophages promote tumour progression and metastasis","volume":"4","author":"JW Pollard","year":"2004","journal-title":"Nature reviews Cancer"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ccr.2013.02.013","article-title":"Macrophage regulation of tumor responses to anticancer therapies","volume":"23","author":"M De Palma","year":"2013","journal-title":"Cancer cell"},{"issue":"4","key":"ref6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1084\/jem.20150295","article-title":"The interaction of anticancer therapies with tumor-associated macrophages","volume":"212","author":"A Mantovani","year":"2015","journal-title":"The Journal of experimental medicine"},{"issue":"6","key":"ref7","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/cncr.21324","article-title":"The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines","volume":"104","author":"G Delaney","year":"2005","journal-title":"Cancer"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2014.00001","article-title":"Radiotherapy and the tumor stroma: the importance of dose and fractionation","volume":"4","author":"T Hellevik","year":"2014","journal-title":"Frontiers in oncology"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.ijrobp.2004.05.065","article-title":"Macrophages enhance the radiosensitizing activity of lipid A: a novel role for immune cells in tumor cell radioresponse","volume":"60","author":"M De Ridder","year":"2004","journal-title":"International journal of radiation oncology, biology, physics"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1158\/0008-5472.CAN-09-2995","article-title":"Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages as a radiosensitizing strategy","volume":"70","author":"Y Meng","year":"2010","journal-title":"Cancer research"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"A Mantovani","year":"2004","journal-title":"Trends in immunology"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","article-title":"Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"A Mantovani","year":"2002","journal-title":"Trends in immunology"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.it.2015.02.004","article-title":"Macrophages and cancer: from mechanisms to therapeutic implications","volume":"36","author":"R Ostuni","year":"2015","journal-title":"Trends in immunology"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1073\/pnas.90.12.5742","article-title":"p53 mutations increase resistance to ionizing radiation","volume":"90","author":"JM Lee","year":"1993","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1365-2184.1996.01009.x","article-title":"p53 mutations associated with increased sensitivity to ionizing radiation in human head and neck cancer cell lines","volume":"29","author":"K Servomaa","year":"1996","journal-title":"Cell proliferation"},{"issue":"2","key":"ref16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/09553002.2014.937511","article-title":"High resistance to X-rays and therapeutic carbon ions in glioblastoma cells bearing dysfunctional ATM associates with intrinsic chromosomal instability","volume":"91","author":"I Dokic","year":"2015","journal-title":"International journal of radiation biology"},{"issue":"6","key":"ref17","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1667\/RR2295.1","article-title":"Alterations in DNA repair efficiency are involved in the radioresistance of esophageal adenocarcinoma","volume":"174","author":"N Lynam-Lennon","year":"2010","journal-title":"Radiation research"},{"issue":"9","key":"ref18","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/S0959-8049(99)00134-3","article-title":"Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells","volume":"35","author":"JU Lee","year":"1999","journal-title":"European journal of cancer"},{"issue":"6","key":"ref19","doi-asserted-by":"crossref","first-page":"e100738","DOI":"10.1371\/journal.pone.0100738","article-title":"Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma","volume":"9","author":"N Lynam-Lennon","year":"2014","journal-title":"PloS one"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fmolb.2014.00024","article-title":"Biological response of cancer cells to radiation treatment","volume":"1","author":"R Baskar","year":"2014","journal-title":"Frontiers in molecular biosciences"},{"issue":"11","key":"ref21","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nrc1735","article-title":"Radiation and the microenvironment\u2014tumorigenesis and therapy","volume":"5","author":"MH Barcellos-Hoff","year":"2005","journal-title":"Nature reviews Cancer"},{"issue":"7","key":"ref22","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nrc3958","article-title":"The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence","volume":"15","author":"HE Barker","year":"2015","journal-title":"Nature reviews Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"18765","DOI":"10.1038\/srep18765","article-title":"Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities","volume":"6","author":"AT Pinto","year":"2016","journal-title":"Scientific reports"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.ijrobp.2008.06.1928","article-title":"Overview of radiosensitivity of human tumor cells to low-dose-rate irradiation","volume":"72","author":"JR Williams","year":"2008","journal-title":"International journal of radiation oncology, biology, physics"},{"issue":"12","key":"ref25","doi-asserted-by":"crossref","first-page":"e82982","DOI":"10.1371\/journal.pone.0082982","article-title":"Comparative analysis of radiosensitizers for K-RAS mutant rectal cancers","volume":"8","author":"LB Kleiman","year":"2013","journal-title":"PloS one"},{"issue":"16","key":"ref26","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1038\/onc.2013.154","article-title":"Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y(1086), c-Src, Erk1\/2 and Akt phosphorylation and smallGTPase activity","volume":"33","author":"AP Cardoso","year":"2014","journal-title":"Oncogene"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1093\/jmcb\/mju045","article-title":"CHK2 kinase in the DNA damage response and beyond","volume":"6","author":"L Zannini","year":"2014","journal-title":"Journal of molecular cell biology"},{"issue":"1\u20132","key":"ref28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2011.12.012","article-title":"Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury","volume":"327","author":"EI Azzam","year":"2012","journal-title":"Cancer letters"},{"issue":"7","key":"ref29","doi-asserted-by":"crossref","first-page":"726","DOI":"10.7150\/ijbs.12009","article-title":"Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming","volume":"11","author":"HH Li","year":"2015","journal-title":"International journal of biological sciences"},{"issue":"11","key":"ref30","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"RA Gatenby","year":"2004","journal-title":"Nature reviews Cancer"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cyto.2012.04.033","article-title":"IL10, IL11, IL18 are differently expressed in CD14+ TAMs and play different role in regulating the invasion of gastric cancer cells under hypoxia","volume":"59","author":"Z Shen","year":"2012","journal-title":"Cytokine"},{"issue":"15","key":"ref32","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1016\/j.ejca.2013.06.005","article-title":"Crosstalk between colon cancer cells and macrophages via inflammatory mediators and CD47 promotes tumour cell migration","volume":"49","author":"Y Zhang","year":"2013","journal-title":"European journal of cancer"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1186\/s12885-015-1546-9","article-title":"M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide","volume":"15","author":"M Genin","year":"2015","journal-title":"BMC cancer"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"9188","DOI":"10.1038\/srep09188","article-title":"Characterization of macrophage\u2014cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer","volume":"5","author":"M Hollmen","year":"2015","journal-title":"Scientific reports"},{"key":"ref35","article-title":"Interactions between colon cancer cells and tumor-infiltrated macrophages depending on cancer cell-derived colony stimulating factor 1","author":"H Wang","year":"2016","journal-title":"OncoImmunology"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cellimm.2014.05.015","article-title":"Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells","volume":"290","author":"TH Wu","year":"2014","journal-title":"Cellular immunology"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"11966","DOI":"10.3390\/ijms160611966","article-title":"Exposure of tumor-associated macrophages to apoptotic MCF-7 cells promotes breast cancer growth and metastasis","volume":"16","author":"N Zhou","year":"2015","journal-title":"International journal of molecular sciences"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"88","DOI":"10.5551\/jat.11.88","article-title":"A comparison of differences in the gene expression profiles of phorbol 12-myristate 13-acetate differentiated THP-1 cells and human monocyte-derived macrophage","volume":"11","author":"T Kohro","year":"2004","journal-title":"Journal of atherosclerosis and thrombosis"},{"issue":"12","key":"ref39","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1158\/0008-5472.CAN-14-0013","article-title":"Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer","volume":"74","author":"D Mouradov","year":"2014","journal-title":"Cancer research"},{"issue":"6199","key":"ref40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/336577a0","article-title":"Localization of an ataxia-telangiectasia gene to chromosome 11q22-23","volume":"336","author":"RA Gatti","year":"1988","journal-title":"Nature"},{"issue":"13","key":"ref41","first-page":"2817","article-title":"Explaining differences in sensitivity to killing by ionizing radiation between human lymphoid cell lines","volume":"58","author":"DR Aldridge","year":"1998","journal-title":"Cancer research"},{"issue":"5","key":"ref42","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.ijrobp.2011.05.057","article-title":"K-RAS(V12) induces autocrine production of EGFR ligands and mediates radioresistance through EGFR-dependent Akt signaling and activation of DNA-PKcs","volume":"81","author":"M Minjgee","year":"2011","journal-title":"International journal of radiation oncology, biology, physics"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0076-6879(01)33063-X","article-title":"Ras regulation of radioresistance in cell culture","volume":"333","author":"AK Gupta","year":"2001","journal-title":"Methods in enzymology"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.radonc.2014.07.015","article-title":"AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells","volume":"112","author":"T Shimura","year":"2014","journal-title":"Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology"},{"issue":"6","key":"ref45","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2307\/3579487","article-title":"Transient increase in glycolytic metabolism in cultured tumor cells immediately after exposure to ionizing radiation: from gene expression to deoxyglucose uptake","volume":"147","author":"Y Fujibayashi","year":"1997","journal-title":"Radiation research"},{"issue":"9","key":"ref46","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/sj.onc.1200927","article-title":"Induction of BCL2 family member MCL1 as an early response to DNA damage","volume":"14","author":"Q Zhan","year":"1997","journal-title":"Oncogene"},{"issue":"24","key":"ref47","first-page":"6348","article-title":"Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells","volume":"54","author":"JE Reynolds","year":"1994","journal-title":"Cancer research"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1210\/me.2011-1282","article-title":"Antiapoptotic signaling via MCL1 confers resistance to caspase-3-mediated apoptotic cell death in the pregnant human uterine myocyte","volume":"26","author":"A Stephenson-Famy","year":"2012","journal-title":"Molecular endocrinology"},{"issue":"3","key":"ref49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4161\/cbt.4.3.1496","article-title":"Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells","volume":"4","author":"L Song","year":"2005","journal-title":"Cancer biology & therapy"},{"issue":"14","key":"ref50","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1128\/MCB.00279-09","article-title":"Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis","volume":"29","author":"C Morel","year":"2009","journal-title":"Molecular and cellular biology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1477-7819-9-117","article-title":"Adenovirus-mediated siRNA targeting Bcl-xL inhibits proliferation, reduces invasion and enhances radiosensitivity of human colorectal cancer cells","volume":"9","author":"J Yang","year":"2011","journal-title":"World journal of surgical oncology"},{"issue":"1","key":"ref52","doi-asserted-by":"crossref","first-page":"e1039763","DOI":"10.1080\/2162402X.2015.1039763","article-title":"Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells","volume":"5","author":"OA Haabeth","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1756-9966-30-62","article-title":"Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer","volume":"30","author":"R Wang","year":"2011","journal-title":"Journal of experimental & clinical cancer research: CR"},{"issue":"5","key":"ref54","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ccell.2014.09.006","article-title":"Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells","volume":"26","author":"B Ruffell","year":"2014","journal-title":"Cancer cell"},{"issue":"6","key":"ref55","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","article-title":"A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes","volume":"10","author":"RM Neve","year":"2006","journal-title":"Cancer cell"},{"issue":"45","key":"ref56","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1038\/sj.onc.1206882","article-title":"Radiation-induced bystander effects, carcinogenesis and models","volume":"22","author":"C Mothersill","year":"2003","journal-title":"Oncogene"},{"issue":"4","key":"ref57","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrc3007","article-title":"Strategies to improve radiotherapy with targeted drugs","volume":"11","author":"AC Begg","year":"2011","journal-title":"Nature reviews Cancer"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0160891","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T23:12:18Z","timestamp":1540336338000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0160891"}},"subtitle":[],"editor":[{"given":"Nils","family":"Cordes","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2016,8,11]]},"references-count":57,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0160891","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,11]]}}}