Dual targeting c-met and VEGFR2 in osteoblasts suppresses growth and osteolysis of prostate cancer bone metastasis
DC Field | Value | Language |
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dc.contributor.author | Lee, Changki | - |
dc.contributor.author | Whang, Young Mi | - |
dc.contributor.author | Campbell, Preston | - |
dc.contributor.author | Mulcrone, Patrick L. | - |
dc.contributor.author | Elefteriou, Florent | - |
dc.contributor.author | Cho, Sun Wook | - |
dc.contributor.author | Park, Serk In | - |
dc.date.accessioned | 2021-09-02T15:06:29Z | - |
dc.date.available | 2021-09-02T15:06:29Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-02-01 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/77406 | - |
dc.description.abstract | Prostate cancer characteristically induces osteoblastic bone metastasis, for which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2 (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in osteoblasts in the context of bone metastasis remain unclear. Here we show using cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased receptor activator of NF kappa B ligand (RANKL) and M-CSF, two essential factors for osteoclastogenesis. Insulin-like growth factor-1 (IGF1) also increased RANKL and M-CSF via c-Met transactivation. The conditioned media from IGF1-, HGF-, or VEGFA-treated osteoblasts promoted osteoclastogenesis that was reversed by inhibiting c-Met and/or VEGFR2 in osteoblasts. In vivo experiments used cabozantinib-resistant prostate cancer cells (PC-3 and C4-2B) to test the effects of c-Met/VEGFR2 inhibition specifically in osteoblasts. Cabozantinib (60 mg/kg, 3 weeks) suppressed tumor growth in bone and reduced expression of RANKL and M-CSF and subsequent tumor-induced osteolysis. Collectively, inhibition of c-Met and VEGFR2 in osteoblasts reduced RANKL and M-CSF expression, and associated with reduction of tumor-induced osteolysis, suggesting that c-Met and VEGFR2 are promising therapeutic targets in bone metastasis. (C) 2017 Elsevier B.V. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER IRELAND LTD | - |
dc.subject | KINASE INHIBITOR | - |
dc.subject | TUMOR-GROWTH | - |
dc.subject | CABOZANTINIB | - |
dc.subject | RECEPTOR | - |
dc.subject | CELLS | - |
dc.subject | SOIL | - |
dc.title | Dual targeting c-met and VEGFR2 in osteoblasts suppresses growth and osteolysis of prostate cancer bone metastasis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Serk In | - |
dc.identifier.doi | 10.1016/j.canlet.2017.11.016 | - |
dc.identifier.scopusid | 2-s2.0-85034992423 | - |
dc.identifier.wosid | 000419810900021 | - |
dc.identifier.bibliographicCitation | CANCER LETTERS, v.414, pp.205 - 213 | - |
dc.relation.isPartOf | CANCER LETTERS | - |
dc.citation.title | CANCER LETTERS | - |
dc.citation.volume | 414 | - |
dc.citation.startPage | 205 | - |
dc.citation.endPage | 213 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | KINASE INHIBITOR | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.subject.keywordPlus | CABOZANTINIB | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | SOIL | - |
dc.subject.keywordAuthor | Prostate cancer | - |
dc.subject.keywordAuthor | Bone metastasis | - |
dc.subject.keywordAuthor | Osteoblasts | - |
dc.subject.keywordAuthor | c-Met | - |
dc.subject.keywordAuthor | VEGFR2 | - |
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