title: IL-22 promotes the proliferation of cancer cells in smoking colorectal cancer patients.
abstract: Chronic cigarette smoking increases the risk of developing colorectal cancer (CRC) and causes higher mortality of CRC patients. To improve our understanding of the underlying mechanism and devise treatment strategies specifically targeted at chronic smoking CRC patients, we examined the immune system of healthy and CRC patients who are complete nonsmokers or chronic primary smokers. We found that the serum concentrations of CRC nonsmokers and CRC smokers were skewed toward Th17-type cytokines, including interleukin (IL)-17 and IL-22. Notably, smoking CRC subjects had significantly higher levels of IL-22 than nonsmoking CRC patients. We also observed higher percentages of CCR4(+)CCR6(+) Th17 cells in circulating blood and higher secretion of IL-17 and IL-22 by peripheral blood mononuclear cells (PBMCs) of nonsmoking CRC and smoking CRC patients, compared to healthy individuals. Again, we observed elevated IL-17 and IL-22 secretion by CRC smokers than nonsmokers. Since IL-22 has been shown to stimulate tumorigenesis, which was also replicated in our experiments using cancer cell line model, we tested whether CRC patients' cell culture supernatant could also support tumor growth using this model. We found that both HT29 cells and LoVo cells had the highest proliferation in the supernatant from smoking CRC patients. Moreover, the proliferation of LoVo cells in smoking CRC supernatant was significantly higher than that in nonsmoking CRC supernatant. In addition, we found that the IL-22 concentration in normal gut tissue of the smoking CRC patients was significantly increased compared to that in nonsmoking CRC subjects, while no significant differences were observed in tumor tissues. Our results suggest that chronic smokers may have higher risk for CRC and worse prognosis due to dysregulated IL-22 production.
authors: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.|Department of oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors: Bao
authors: B
authors: Song
authors: Department of oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors: Yuan
authors: Y
authors: Ma
authors: Department of oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors: Xiuchun
authors: X
authors: Liu
authors: Department of oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, Shandong, 250117, China.
authors: Wanhu
authors: W
authors: Li
authors: Department of pathology, Shandong Cancer Hospital and Institute, Jinan, China.
authors: Jianbo
authors: J
authors: Zhang
authors: Department of oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, Shandong, 250117, China. liujiesdch@126.com.
authors: Jie
authors: J
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China. jinxianghan_jn@sina.com.|Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, China. jinxianghan_jn@sina.com.
authors: Jinxiang
authors: J
authors: Han
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22; C508717:IL17A protein, human
keywords: Colorectal cancer; IL-22; Smoking