Cited 84 times in
Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization
DC Field | Value | Language |
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dc.contributor.author | 조재호 | - |
dc.date.accessioned | 2019-01-15T17:06:22Z | - |
dc.date.available | 2019-01-15T17:06:22Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/166809 | - |
dc.description.abstract | It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour vasculature with abnormal SMA+NG2+ pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6+ cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6+ cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1+ TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Transdifferentiation/drug effects | - |
dc.subject.MESH | Cell Transdifferentiation/genetics | - |
dc.subject.MESH | Endothelial Cells/metabolism* | - |
dc.subject.MESH | Epithelial-Mesenchymal Transition/genetics | - |
dc.subject.MESH | Epithelial-Mesenchymal Transition/physiology* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Heterocyclic Compounds/pharmacology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Hyaluronan Receptors/metabolism* | - |
dc.subject.MESH | Immunohistochemistry | - |
dc.subject.MESH | Macrophages/metabolism* | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred BALB C | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Neoplastic Stem Cells/metabolism | - |
dc.subject.MESH | Receptor, Transforming Growth Factor-beta Type II/genetics | - |
dc.subject.MESH | Receptor, Transforming Growth Factor-beta Type II/metabolism | - |
dc.subject.MESH | Receptors, CXCR4/genetics | - |
dc.subject.MESH | Receptors, CXCR4/metabolism | - |
dc.subject.MESH | Signal Transduction/genetics | - |
dc.subject.MESH | Signal Transduction/physiology | - |
dc.title | Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Radiation Oncology (방사선종양학교실) | - |
dc.contributor.googleauthor | Seo-Hyun Choi | - |
dc.contributor.googleauthor | A-Ram Kim | - |
dc.contributor.googleauthor | Jae-Kyung Nam | - |
dc.contributor.googleauthor | Jin-Mo Kim | - |
dc.contributor.googleauthor | Jee-Youn Kim | - |
dc.contributor.googleauthor | Haeng Ran Seo | - |
dc.contributor.googleauthor | Hae-June Lee | - |
dc.contributor.googleauthor | Jaeho Cho | - |
dc.contributor.googleauthor | Yoon-Jin Lee | - |
dc.identifier.doi | 10.1038/s41467-018-07470-w | - |
dc.contributor.localId | A03901 | - |
dc.relation.journalcode | J02293 | - |
dc.identifier.eissn | 2041-1723 | - |
dc.identifier.pmid | 30504836 | - |
dc.contributor.alternativeName | Cho, Jae Ho | - |
dc.contributor.affiliatedAuthor | 조재호 | - |
dc.citation.volume | 9 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 5108 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, Vol.9(1) : 5108, 2018 | - |
dc.identifier.rimsid | 58186 | - |
dc.type.rims | ART | - |
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