HMGB1 released by irradiated tumor cells promotes living tumor cell proliferation via paracrine effect

• DOI: 10.1038/s41419-018-0626-6
• Publication Date: 2018-05-29T10:07:37Z
• Authors: Sijia He; Jin Cheng; Lianhui Sun; Yiwei Wang; Chuangui Wang; Xinjian Liu; Zhengxiang Zhang; Minghui Zhao; Yuntao Luo; Ling Tian; Chuanyuan Li; Qian Huang
• Keywords: Male; 0303 health sciences; Cell Survival; MAP Kinase Signaling System; Middle Aged; Prognosis; Survival Analysis; Article; 3. Good health; 03 medical and health sciences; Antigens, Neoplasm; Cell Line, Tumor; Neoplasms; Multivariate Analysis; Paracrine Communication; Humans; Female; HMGB1 Protein; Mitogen-Activated Protein Kinases; Cell Proliferation; Protein Binding

AbstractTumor repopulation during therapy is an important cause of treatment failure. Strategies to overcome repopulation are arising in parallel with advances in the comprehension of underlying biological mechanisms. Here, we reveal a new mechanism by which high mobility group box 1 (HMGB1) released by dying cells during radiotherapy or chemotherapy could stimulate living tumor cell proliferationInhibition or genetic ablation of HMGB1 suppressed tumor cell proliferation. This effect was due to binding of HMGB1with the member receptor for advanced glycation end-products (RAGE), which activated downstream ERK and p38 signaling pathway and promoted cell proliferation. Furthermore, higher HMGB1 expression in tumor tissue correlated with poor overall survival and higher HMGB1 concentration was detected in serum of patients who accepted radiotherapy. Collectively, the results from this study suggested that interaction between dead cells and surviving cells might influence the fate of tumor. HMGB1 could be a novel tumor promoter with therapeutic and prognostic relevance in cancers.