title: Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer.
abstract: The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of general surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China.
authors.forename: Yongxu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Shoubo
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Dehai
authors.initials: D
authors.lastname: Che
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C502451:CCDC88A protein, human; D017077:Culture Media, Conditioned; D016207:Cytokines; D020381:Interleukin-17; D008840:Microfilament Proteins; D012333:RNA, Messenger; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins