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, Yoon Jin Lee

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32 Citations (Scopus)


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.

Original languageEnglish
Article number5108
JournalNature communications
Issue number1
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation (NRF-2013M2A2A7043580, NRF-2017M2A2A7A02019482, and NRF-2017R1A2B2004156), as well as a grant from the Korea Institute of Radiological & Medical Sciences (KIRAMS, 50531–2018) funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

Publisher Copyright:
© 2018, The Author(s).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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