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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 |
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dc.contributor.author | 강규섭 | - |
dc.contributor.author | 강숙희 | - |
dc.contributor.author | 고명청 | - |
dc.contributor.author | 김백길 | - |
dc.contributor.author | 박행란 | - |
dc.contributor.author | 조남훈 | - |
dc.contributor.author | 최윤표 | - |
dc.date.accessioned | 2014-12-19T16:35:14Z | - |
dc.date.available | 2014-12-19T16:35:14Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 1465-5411 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/89810 | - |
dc.description.abstract | INTRODUCTION: 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.statementOfResponsibility | open | - |
dc.relation.isPartOf | BREAST CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling. | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Yonsei Biomedical Research Center (연세의생명연구원) | - |
dc.contributor.googleauthor | Baek Gil Kim | - |
dc.contributor.googleauthor | Ming-Qing Gao | - |
dc.contributor.googleauthor | Yoon Pyo Choi | - |
dc.contributor.googleauthor | Suki Kang | - |
dc.contributor.googleauthor | Haeng Ran Park | - |
dc.contributor.googleauthor | Kyu Sub Kang | - |
dc.contributor.googleauthor | Nam Hoon Cho | - |
dc.identifier.doi | 10.1186/bcr3203 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00005 | - |
dc.contributor.localId | A00044 | - |
dc.contributor.localId | A00116 | - |
dc.contributor.localId | A00484 | - |
dc.contributor.localId | A01731 | - |
dc.contributor.localId | A03812 | - |
dc.contributor.localId | A04143 | - |
dc.relation.journalcode | J00402 | - |
dc.identifier.eissn | 1465-542X | - |
dc.contributor.alternativeName | Kang, Kyu Sub | - |
dc.contributor.alternativeName | Kang, Suki | - |
dc.contributor.alternativeName | Gao, Ming Qing | - |
dc.contributor.alternativeName | Kim, Baek Gil | - |
dc.contributor.alternativeName | Park, Haeng Ran | - |
dc.contributor.alternativeName | Cho, Nam Hoon | - |
dc.contributor.alternativeName | Choi, Yoon Pyo | - |
dc.contributor.affiliatedAuthor | Kang, Kyu Sub | - |
dc.contributor.affiliatedAuthor | Kang, Suki | - |
dc.contributor.affiliatedAuthor | Gao, Ming Qing | - |
dc.contributor.affiliatedAuthor | Kim, Baek Gil | - |
dc.contributor.affiliatedAuthor | Park, Haeng Ran | - |
dc.contributor.affiliatedAuthor | Cho, Nam Hoon | - |
dc.contributor.affiliatedAuthor | Choi, Yoon Pyo | - |
dc.citation.volume | 14 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 88 | - |
dc.identifier.bibliographicCitation | BREAST CANCER RESEARCH, Vol.14(3) : 88, 2012 | - |
dc.identifier.rimsid | 31920 | - |
dc.type.rims | ART | - |
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