title: Interleukin 23 regulates proliferation of lung cancer cells in a concentration-dependent way in association with the interleukin-23 receptor.
abstract: A proinflammatory cytokine, interleukin 23 (IL-23), plays a role in tumor progression by inducing inflammation in the tumor microenvironment, although there is debate about its role in carcinogenesis. Direct effects of IL-23 on tumor cells have been reported rarely, and contradictory effects have been observed. Here, we studied such effects of IL-23 in lung cancer cells in vitro and in vivo and explored the underlying mechanism. We found IL-23 receptor expression in tissues from lung adenocarcinoma and small cell carcinoma but not in lung squamous cell carcinoma tissue. Interestingly, different concentrations of IL-23 had opposite effects in the same types of cells. We confirmed that the different effects could be explained by differences in binding to the IL-23 receptor (subunits IL-23r and IL-12Rβ1). Low concentrations of IL-23 promoted the proliferation of IL-23 receptor-positive A549 and SPCA-1 lung cancer cells by binding to IL-23r, whereas high concentrations of IL-23 inhibited proliferation of these cells by binding to both IL-23r and IL-12Rβ1. In contrast, IL-23 had no effect on IL-23 receptor-negative SK-MES-1 cells. IL-23 regulated the growth of human lung cancer cells through its effects on STAT3 expression and phosphorylation in a concentration-dependent way; the Ki-67 gene was involved in these processes. Our findings demonstrate for the first time that IL-23 affects the proliferation of IL-23 receptor-positive lung cancer cells and that this effect is dependent on the IL-23 concentration. This can explain at least part of the inconsistent reports on the role of IL-23 in the progression of carcinogenesis.
authors.affiliation: Division of Geriatrics, Center for Medical Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Wei
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Lugang
authors.initials: L
authors.lastname: Huang
authors.forename: Sen
authors.initials: S
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Xiujie
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000818:Animals; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D053759:Interleukin-23 / Q000494:pharmacology / Q000502:physiology*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D018123:Receptors, Interleukin / Q000378:metabolism / Q000502:physiology*; D053707:Receptors, Interleukin-12 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: C508438:IL12RB1 protein, human; C515500:IL23R protein, human; D053759:Interleukin-23; D019394:Ki-67 Antigen; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human