Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization

Seo-Hyun Choi, A-Ram Kim, Jae-Kyung Nam, Jin-Mo Kim, Jee-Youn Kim, Haeng Ran Seo, Hae-June Lee, Jaeho Cho and Yoon-Jin Lee ()
Additional contact information
Seo-Hyun Choi: Korea Institute of Radiological & Medical Sciences
A-Ram Kim: Korea Institute of Radiological & Medical Sciences
Jae-Kyung Nam: Korea Institute of Radiological & Medical Sciences
Jin-Mo Kim: Yonsei University College of Medicine
Jee-Youn Kim: Yonsei University College of Medicine
Haeng Ran Seo: Institute Pasteur Korea
Hae-June Lee: Korea Institute of Radiological & Medical Sciences
Jaeho Cho: Yonsei University College of Medicine
Yoon-Jin Lee: Korea Institute of Radiological & Medical Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07470-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07470-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07470-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().