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IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor

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dc.contributor.author김원호-
dc.contributor.author김태일-
dc.contributor.author박수정-
dc.contributor.author박재준-
dc.contributor.author천재희-
dc.date.accessioned2021-09-29T00:42:26Z-
dc.date.available2021-09-29T00:42:26Z-
dc.date.issued2021-03-
dc.identifier.issn0899-1987-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/183996-
dc.description.abstractInteraction between a tumor and its microenvironment is important for tumor initiation and progression. Cancer stem cells (CSCs) within the tumor interact with a microenvironmental niche that controls their maintenance and differentiation. We investigated the CSC-promoting effect of factors released from myofibroblasts into the microenvironment of early colorectal cancer tumors and its molecular mechanism. By messenger RNA microarray analysis, expression of HES1, a Notch signaling target, significantly increased in Caco-2 cells cocultured with 18Co cells (pericryptal myofibroblasts), compared to its expression in Caco-2 cells cultured alone. Caco-2 cells cultured in 18Co-conditioned media (CM) showed a significant increase in CD133+CD44+ cells and HES1 expression compared to that in Caco-2 cells cultured in regular media. Significant amounts of interleukin-6 (IL-6) and IL-8 were detected in 18Co-CM compared to levels in regular media. The 18Co-CM-induced increase in CD133+CD44+ cells was attenuated by IL-6- and IL-8-neutralizing antibodies. Furthermore, these neutralizing antibodies and inhibitors of STAT3 and gamma-secretase reduced the expression of HES1 induced in Caco-2 cells cultured in 18Co-CM. Immunohistochemical analysis of human tissues revealed that IL-6, IL-8, and HES1 expression increased from normal to adenoma, and from adenoma to cancer tissues. In addition, IL-6 and HES1 expression was positively correlated in early colorectal cancer tissues. In conclusion, the increase of CSCs by myofibroblasts could be mediated by IL-6/IL-8-induced HES1 activation in the tumor microenvironment. Based on these data, the IL-6/IL-8-mediated Notch/HES1 and STAT3 pathway, through which CSCs interact with their microenvironment, might be a potential target for the prevention and treatment of colorectal tumors.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherWiley-Liss-
dc.relation.isPartOfMOLECULAR CARCINOGENESIS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHCaco-2 Cells-
dc.subject.MESHColorectal Neoplasms / genetics-
dc.subject.MESHColorectal Neoplasms / metabolism-
dc.subject.MESHColorectal Neoplasms / pathology*-
dc.subject.MESHCulture Media, Conditioned / pharmacology-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHHumans-
dc.subject.MESHInterleukin-6 / metabolism*-
dc.subject.MESHInterleukin-8 / metabolism*-
dc.subject.MESHMyofibroblasts / metabolism-
dc.subject.MESHMyofibroblasts / pathology-
dc.subject.MESHNeoplastic Stem Cells / drug effects-
dc.subject.MESHNeoplastic Stem Cells / metabolism-
dc.subject.MESHNeoplastic Stem Cells / pathology*-
dc.subject.MESHOrganoids / pathology-
dc.subject.MESHSTAT3 Transcription Factor / antagonists & inhibitors-
dc.subject.MESHSTAT3 Transcription Factor / metabolism-
dc.subject.MESHTranscription Factor HES-1 / genetics-
dc.subject.MESHTranscription Factor HES-1 / metabolism*-
dc.subject.MESHTumor Microenvironment / drug effects-
dc.titleIL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorBun Kim-
dc.contributor.googleauthorYoojeong Seo-
dc.contributor.googleauthorJi-Hee Kwon-
dc.contributor.googleauthorYoumi Shin-
dc.contributor.googleauthorSuhyun Kim-
dc.contributor.googleauthorSoo Jung Park-
dc.contributor.googleauthorJae Jun Park-
dc.contributor.googleauthorJae Hee Cheon-
dc.contributor.googleauthorWon Ho Kim-
dc.contributor.googleauthorTae Il Kim-
dc.identifier.doi10.1002/mc.23283-
dc.contributor.localIdA00774-
dc.contributor.localIdA01079-
dc.contributor.localIdA01539-
dc.contributor.localIdA01636-
dc.contributor.localIdA04030-
dc.relation.journalcodeJ02255-
dc.identifier.eissn1098-2744-
dc.identifier.pmid33544929-
dc.identifier.urlhttps://onlinelibrary.wiley.com/doi/10.1002/mc.23283-
dc.subject.keywordHES1-
dc.subject.keywordIL-6-
dc.subject.keywordIL-8-
dc.subject.keywordcancer stem cell-
dc.subject.keywordcolorectal cancer-
dc.subject.keywordmyofibroblast-
dc.contributor.alternativeNameKim, Won Ho-
dc.contributor.affiliatedAuthor김원호-
dc.contributor.affiliatedAuthor김태일-
dc.contributor.affiliatedAuthor박수정-
dc.contributor.affiliatedAuthor박재준-
dc.contributor.affiliatedAuthor천재희-
dc.citation.volume60-
dc.citation.number3-
dc.citation.startPage188-
dc.citation.endPage200-
dc.identifier.bibliographicCitationMOLECULAR CARCINOGENESIS, Vol.60(3) : 188-200, 2021-03-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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