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

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 (TA

SUBMITTER: Choi SH 

PROVIDER: S-EPMC6269447 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature