title: Interleukin-17 potently increases non-small cell lung cancer growth.
abstract: The aim of the present study was to explore the effects of interleukin (IL)-17 on the growth and metastasis of tumors that were subcutaneously implanted into C57BL/6 mice. Lewis lung carcinoma (LLC) cells were subcutaneously injected into C57BL/6 mice followed by intraperitoneal injection of mouse recombinant IL-17 protein (IL-17 groups) or phosphate-buffered saline (control groups). Tumor growth and metastasis were assessed by measuring the size and weight of tumors and cervical lymph nodes, respectively. Cytokine expression in tumor masses was quantified by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. CCR2-positive macrophage infiltration in tumor masses was detected by flow cytometric analysis. The proliferation and migration of LLC cells, stimulated by the IL-17 protein were detected by Cell Counting kit (CCK)-8 and wound scratch assays in vitro. Tumors were grafted into the C57BL/6 mice. The mice that were intraperitoneally injected with IL-17 exhibited significantly larger tumors compared with the control mice. After day 7 of injection and beyond, the weight of cervical lymph nodes in IL-17 groups was higher than that in the control mice. It was also demonstrated that the number of CCR2-positive macrophages that infiltrated the tumor masses in the IL-17 groups was higher than that of the control mice. CD34 expression in vascular endothelial cells was also higher in tumors grafted in IL-17 mice than those grafted in control mice. Furthermore, the tumor tissue mRNA and protein expression levels of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and tumor necrosis factor-α were greater in mice from the IL-17 group than the control mice, while levels of migration inhibitory factor and thrombospondin-1 were lower in mice from the IL-17 group than in the control. IL-17 also increased the migration of LLC cells in vitro. In conclusion, IL-17 exhibited the ability to promote tumor growth by increasing angiogenesis, metastasis and increasing CCR2+ macrophage infiltration into tumors.
authors.affiliation: Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215002, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215002, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215002, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215002, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu 215002, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D020381:Interleukin-17 / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D054390:Receptors, CCR2 / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C515335:Ccr2 protein, mouse; D020381:Interleukin-17; D008263:Macrophage Migration-Inhibitory Factors; D054390:Receptors, CCR2; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse