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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article number5108
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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macrophages
Macrophages
Radiotherapy
Tumors
radiation therapy
tumors
cancer
Cells
Polarization
polarization
Neoplasms
deletion
Endothelial cells
Radiation
Endothelial Cells
radiation
spectral mixture analysis
Pericytes
Osteopontin
Neoplastic Stem Cells

All Science Journal Classification (ASJC) codes

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

Cite this

Choi, Seo Hyun ; Kim, A. Ram ; Nam, Jae Kyung ; Kim, Jin Mo ; Kim, Jee Youn ; Seo, Haeng Ran ; Lee, Hae June ; Cho, Jaeho ; Lee, Yoon Jin. / Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization. In: Nature communications. 2018 ; Vol. 9, No. 1.
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Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization. / Choi, Seo Hyun; Kim, A. Ram; Nam, Jae Kyung; Kim, Jin Mo; Kim, Jee Youn; Seo, Haeng Ran; Lee, Hae June; Cho, Jaeho; Lee, Yoon Jin.

In: Nature communications, Vol. 9, No. 1, 5108, 01.12.2018.

Research output: Contribution to journalArticle

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