IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma

Cancer Communications

Qing-qing Cai¹  Zhong-jun Xia¹  Liang Wang¹  Yu-jia Zhu²  Qiu-yu Lai³  Ying-zhi He⁴  Xi-wen Bi⁴ 

[1] Department of Hematology, ZhuJiang Hospital, Southern Medical University, Guangzhou, P. R. China;Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China;Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China

关键词: Natural killer/T-cell lymphoma;    Latent membrane protein 1;    Epstein–Barr virus;    Interleukin-2 receptor alpha;   

DOI  :  10.1186/s40880-018-0334-8

学科分类：肿瘤学

来源: Springer

【 摘 要 】

Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive non-Hodgkin lymphoma often resistant to chemotherapy. Serum level of soluble IL-2 receptor α (IL-2Rα) is elevated in NKTCL patients and correlates significantly with treatment response and survival. In the current study we examined the potential role of IL-2Rα by over-expressing IL-2Rα in representative cell lines. Levels of IL-2Rα were evaluated in the human natural killer cell line NK-92 and the NKTCL cell line SNK-6. Lentiviral vectors were used to express latent membrane protein 1 (LMP1) in NK-92 cells, and IL-2Rα in both NK-92 and SNK-6 cells. The biological effects of these genes on proliferation, apoptosis, cell cycle distribution, and chemosensitivity were analyzed. Expression of IL-2Rα was significantly higher in SNK-6 cells than in NK-92 cells. Expressing LMP1 in NK-92 cells remarkably up-regulated IL-2Rα levels, whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα. IL-2Rα overexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution, and induced resistance to gemcitabine, doxorubicin, and asparaginase. These effects were reversed by an anti-IL-2Rα antibody. Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells, up-regulating IL-2Rα expression. IL-2Rα overexpression promotes growth and chemoresistance in NKTCL, making this interleukin receptor a potential therapeutic target.

【 授权许可】

CC BY