期刊
JOURNAL OF THORACIC ONCOLOGY
卷 8, 期 8, 页码 1032-1042出版社
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0b013e31829923c8
关键词
Lung cancer; Small-cell lung cancer; Large-cell lung cancer; Interleukin-22; Interleukin-22-receptor 1
资金
- Bayerisches Immuntherapienetzwerk (BayImmunet)
- Curt-Bohnewand Fond
- Friedrich Baur Stiftung
- Programm zur Forderung von Forschung und Lehre (FoFoLe) der Medizinischen Fakultat der Ludwig-Maximilians Universitat Munchen
- Deutsche Forschungsgemeinschaft
- [Graduiertenkolleg 1202]
Introduction: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients. Methods: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay. Results: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed. Conclusion: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype.
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