Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor.

Abstract

Repopulation of residual tumor cells impedes curative radiotherapy, yet the mechanism is not fully understood. It is recently appreciated that cancer cells adopt a transient persistence to survive the stress of chemo- or targeted therapy and facilitate eventual relapse. Here, it is shown that cancer cells likewise enter a "radiation-tolerant persister" (RTP) state to evade radiation pressure in vitro and in vivo. RTP cells are characterized by enlarged cell size with complex karyotype, activated type I interferon pathway and two gene patterns represented by CST3 and SNCG. RTP cells have the potential to regenerate progenies via viral budding-like division, and type I interferon-mediated antiviral signaling impaired progeny production. Depleting CST3 or SNCG does not attenuate the formation of RTP cells, but can suppress RTP cells budding with impaired tumor repopulation. Interestingly, progeny cells produced by RTP cells actively lose their aberrant chromosomal fragments and gradually recover back to a chromosomal constitution similar to their unirradiated parental cells. Collectively, this study reveals a novel mechanism of tumor repopulation, i.e., cancer cell populations employ a reversible radiation-persistence by poly- and de-polyploidization to survive radiotherapy and repopulate the tumor, providing a new therapeutic concept to improve outcome of patients receiving radiotherapy.

• Authors: Yucui Zhao, Tingting Lu, Yanwei Song, Yanqin Wen, Zheng Deng, Jiahui Fan, Minghui Zhao, Ruyi Zhao, Yuntao Luo, Jianzhu Xie, Binjie Hu, Haoran Sun, Yiwei Wang, Sijia He, Yanping Gong, Jin Cheng, Xinjian Liu, Liang Yu, Jikun Li, Chuanyuan Li, Yongyong Shi, Qian Huang
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 10 Issue 8 Pg. e2204177 (03 2023) ISSN: 2198-3844 [Electronic] Germany
• PMID: 36658726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Topics

• Humans
• Cell Line, Tumor
• Neoplasms (radiotherapy)