title: JAK2/STAT3 signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer.
abstract: We investigated the clinical significance of Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) during angiogenesis in non-small-cell lung carcinoma. JAK2, phospho-JAK2 (pJAK2), STAT3, and phospho-STAT3 (pSATA3) were observed in 40/68 (58.8%), 39/68 (57.4%), 49/68 (72.1%) and 40/68 (58.8%) of the cases. The high expression levels of molecules involved in the JAK2/STAT3 signaling pathway were associated with a decreased survival rate. Of the total number of cases, 73.5% were positive for VEGF and 80.9% for bFGF. Microvessel density (MVD), as determined by CD34 staining and morphology, was higher in NSCLC samples with high pJAK2 and pSTAT3 expression, and the patients with high MVD had poor survival status. In addition, the expression of pSTAT3 correlated with VEGF (r=0.593) and bFGF (r=0.519) (p<0.05). Inhibiting JAK2 and knocking down STAT3 both suppressed STAT3 activation and reduced the expression of VEGF and bFGF in A549 and NCI-H292 cells, demonstrating that STAT3 activation was associated with VEGF and bFGF expression in the two human lung carcinoma cell lines. Therefore, STAT3 may be a critical molecular target for powerful intervention in NSCLC anti-angiogenesis therapy.
authors.affiliation: Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai 201900, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
authors.forename: Jiong-Yi
authors.initials: JY
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Yuan
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D053614:Janus Kinase 2