IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma
Abstract Background 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 stud...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-10-01
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| Series: | Cancer Communications |
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| Online Access: | http://link.springer.com/article/10.1186/s40880-018-0334-8 |
| _version_ | 1818690359831560192 |
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| author | Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia Qing-qing Cai |
| author_facet | Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia Qing-qing Cai |
| author_sort | Liang Wang |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-17T12:24:45Z |
| format | Article |
| id | doaj.art-347979613dbe49548b626c03f143d9d1 |
| institution | Directory Open Access Journal |
| issn | 2523-3548 |
| language | English |
| last_indexed | 2024-12-17T12:24:45Z |
| publishDate | 2018-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Communications |
| spelling | doaj.art-347979613dbe49548b626c03f143d9d12022-12-21T21:48:48ZengWileyCancer Communications2523-35482018-10-0138111010.1186/s40880-018-0334-8IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphomaLiang Wang0Xi-wen Bi1Yu-jia Zhu2Ying-zhi He3Qiu-yu Lai4Zhong-jun Xia5Qing-qing Cai6Department of Hematology, ZhuJiang Hospital, Southern Medical UniversityState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineDepartment of Hematology, ZhuJiang Hospital, Southern Medical UniversityDepartment of Hematology, ZhuJiang Hospital, Southern Medical UniversityState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineAbstract Background 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. Methods 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s40880-018-0334-8Natural killer/T-cell lymphomaLatent membrane protein 1Epstein–Barr virusInterleukin-2 receptor alpha |
| spellingShingle | Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia Qing-qing Cai 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 Natural killer/T-cell lymphoma Latent membrane protein 1 Epstein–Barr virus Interleukin-2 receptor alpha |
| title | IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma |
| title_full | IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma |
| title_fullStr | IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma |
| title_full_unstemmed | IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma |
| title_short | IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma |
| title_sort | il 2rα up regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer t cell lymphoma |
| topic | Natural killer/T-cell lymphoma Latent membrane protein 1 Epstein–Barr virus Interleukin-2 receptor alpha |
| url | http://link.springer.com/article/10.1186/s40880-018-0334-8 |
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