Tumour-vasculature Development Via Endothelial-to-mesenchymal Transition After Radiotherapy Controls CD44v6 Cancer Cell and Macrophage Polarization

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Dec 4

PMID 30504836

Citations 62

Authors

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

Affiliations

Soon will be listed here.

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 SMANG2 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.

Citing Articles

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