A Selective FGFR inhibitor AZD4547 suppresses RANKL/M-CSF/OPG-dependent ostoclastogenesis and breast cancer growth in the metastatic bone microenvironment
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Jinho | - |
dc.contributor.author | Choi, Yoon Ji | - |
dc.contributor.author | Seo, Bo Yeon | - |
dc.contributor.author | Jo, Ukhyun | - |
dc.contributor.author | Park, Serk In | - |
dc.contributor.author | Kim, Yeul Hong | - |
dc.contributor.author | Park, Kyong Hwa | - |
dc.date.accessioned | 2021-09-01T13:40:03Z | - |
dc.date.available | 2021-09-01T13:40:03Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2019-06-19 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/64746 | - |
dc.description.abstract | Aberrant activation of fibroblast growth factor receptor (FGFR) signalling contributes to progression and metastasis of many types of cancers including breast cancer. Accordingly, FGFR targeted tyrosine kinase inhibitors (TKIs) are currently under development. However, the efficacy of FGFR TKIs in the bone microenvironment where breast cancer cells most frequently metastasize and also where FGFR is biologically active, has not been clearly investigated. We investigated the FGFR-mediated interactions among cancer and the bone microenvironment stromal cells (osteoblasts and osteoclasts), and also the effects of FGFR inhibition in bone metastasis. We showed that addition of culture supernatant from the MDA-MB-134-VI FGFR-amplified breast cancer cells-activated FGFR siganalling in osteoblasts, including increased expression of RANKL, M-CSF, and osteoprotegerin (OPG). Further in vitro analyses showed that AZD4547, an FGFR TKI currently in clinical trials for breast cancer, decreased RANKL and M-CSF, and subsequently RANKL and M-CSF-dependent osteoclastogenesis of murine bone marrow monocytes. Moreover, AZD4547 suppressed osteoclastogenesis and tumor-induced osteolysis in an orthotopic breast cancer bone metastasis mouse model using FGFR non-amplified MDA-MB-231 cells. Collectively, our results support that FGFR inhibitors inhibit the bone microenvironment stromal cells including osteoblasts and osteoclasts, and effectively suppress both tumor and stromal compartments of bone metastasis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | 1 GENE AMPLIFICATION | - |
dc.subject | DOVITINIB TKI258 | - |
dc.subject | EXPRESSION | - |
dc.subject | MECHANISMS | - |
dc.subject | PATHWAYS | - |
dc.subject | TARGET | - |
dc.subject | CELLS | - |
dc.title | A Selective FGFR inhibitor AZD4547 suppresses RANKL/M-CSF/OPG-dependent ostoclastogenesis and breast cancer growth in the metastatic bone microenvironment | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Yoon Ji | - |
dc.contributor.affiliatedAuthor | Park, Serk In | - |
dc.contributor.affiliatedAuthor | Kim, Yeul Hong | - |
dc.contributor.affiliatedAuthor | Park, Kyong Hwa | - |
dc.identifier.doi | 10.1038/s41598-019-45278-w | - |
dc.identifier.scopusid | 2-s2.0-85067817512 | - |
dc.identifier.wosid | 000472029100005 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.9 | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 9 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | 1 GENE AMPLIFICATION | - |
dc.subject.keywordPlus | DOVITINIB TKI258 | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | CELLS | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.