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Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling.

DC Field Value Language
dc.contributor.author강규섭-
dc.contributor.author강숙희-
dc.contributor.author고명청-
dc.contributor.author김백길-
dc.contributor.author박행란-
dc.contributor.author조남훈-
dc.contributor.author최윤표-
dc.date.accessioned2014-12-19T16:35:14Z-
dc.date.available2014-12-19T16:35:14Z-
dc.date.issued2012-
dc.identifier.issn1465-5411-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/89810-
dc.description.abstractINTRODUCTION: Although development of anoikis-resistant myofibroblasts during tissue remodeling is known to be associated with tumor invasion, the mechanism by which myofibroblasts become resistant to anoikis is unknown. We previously demonstrated laminin-332 upregulation in the fibrosis around invasive ductal carcinoma (IDC). Because laminin-332 promotes cell survival through binding to integrins, we hypothesized that invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts by upregulating laminin-332 expression during tissue remodeling. Here, we demonstrate that invasive breast cancer cells induce laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype. METHODS: Three types of fibroblasts were isolated from the tumor burden, the fibrosis, and normal tissue of patients with early stage IDC (less than 10 mm diameter), designated cancer-associated fibroblasts (CAFs), interface fibroblasts (InFs), and normal breast fibroblasts (NBFs), respectively. To investigate direct and indirect crosstalk with tumor cells, fibroblasts were co-cultured with invasive MDA-MB-231 or noninvasive MCF7 cells or in conditioned medium. Anoikis resistance of fibroblasts was measured by cell viability and caspase-3 activity after incubation on poly-HEMA coated plates for 72 hours. Involvement of laminin-332/integrin α3β1 or α6β4 signaling in anoikis resistance was confirmed by treatment with purified laminin-332 or blocking antibodies against laminin-332, integrin β1, or integrin β4. RESULTS: MDA-MB-231 cells induced laminin-332 upregulation and integrin β4 neoexpression in fibroblasts, leading to anoikis resistance. InFs showed a higher endogenous level of laminin-332 than did CAFs and NBFs. After stimulation with MDA-MB-231-conditioned medium, laminin-332 expression of InFs was dramatically increased and maintained under anoikis conditions. Laminin-332 upregulation was also observed in CAFs and NBFs, but at a lower level than in InFs. Laminin-332 induced Akt (Ser473) phosphorylation by binding to integrin α3β1. Integrin β4 neoexpression induced laminin-332-independent Rac1 activation and promoted anoikis resistance in fibroblasts approximately twofold more effectively than did laminin-332, regardless of the type of fibroblast. In addition, integrin β4 expression suppressed fibroblast aggregation in conditions of anoikis. CONCLUSION: Invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin β4 neoexpression. Interface fibroblasts appear to be the primary myofibroblasts that interact with invasive tumor cells during tissue remodeling.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfBREAST CANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleInvasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorBaek Gil Kim-
dc.contributor.googleauthorMing-Qing Gao-
dc.contributor.googleauthorYoon Pyo Choi-
dc.contributor.googleauthorSuki Kang-
dc.contributor.googleauthorHaeng Ran Park-
dc.contributor.googleauthorKyu Sub Kang-
dc.contributor.googleauthorNam Hoon Cho-
dc.identifier.doi10.1186/bcr3203-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00005-
dc.contributor.localIdA00044-
dc.contributor.localIdA00116-
dc.contributor.localIdA00484-
dc.contributor.localIdA01731-
dc.contributor.localIdA03812-
dc.contributor.localIdA04143-
dc.relation.journalcodeJ00402-
dc.identifier.eissn1465-542X-
dc.contributor.alternativeNameKang, Kyu Sub-
dc.contributor.alternativeNameKang, Suki-
dc.contributor.alternativeNameGao, Ming Qing-
dc.contributor.alternativeNameKim, Baek Gil-
dc.contributor.alternativeNamePark, Haeng Ran-
dc.contributor.alternativeNameCho, Nam Hoon-
dc.contributor.alternativeNameChoi, Yoon Pyo-
dc.contributor.affiliatedAuthorKang, Kyu Sub-
dc.contributor.affiliatedAuthorKang, Suki-
dc.contributor.affiliatedAuthorGao, Ming Qing-
dc.contributor.affiliatedAuthorKim, Baek Gil-
dc.contributor.affiliatedAuthorPark, Haeng Ran-
dc.contributor.affiliatedAuthorCho, Nam Hoon-
dc.contributor.affiliatedAuthorChoi, Yoon Pyo-
dc.citation.volume14-
dc.citation.number3-
dc.citation.startPage88-
dc.identifier.bibliographicCitationBREAST CANCER RESEARCH, Vol.14(3) : 88, 2012-
dc.identifier.rimsid31920-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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