Interleukin 7/interleukin 7 receptor induce c-Fos/c-Jun-dependent vascular endothelial growth factor-D up-regulation: a mechanism of lymphangiogenesis in lung cancer.
Interleukin 7 (IL-7) is known to promote lymphangiogenesis. To study the relationship between IL-7 and the lymphangiogenic factor, vascular endothelial growth factor (VEGF)-D, in human lung cancer cells and its impact on the prognosis of lung cancer patients, we investigated how IL-7 regulates VEGF-D. We found that, in lung cancer cell lines, IL-7/IL-7 receptor (IL-7R) increase the expression of VEGF-D and phosphorylation of c-Fos/c-Jun, induce c-Fos and c-Jun heterodimer formation, and enhance c-Fos/c-Jun DNA binding activity to regulate VEGF-D. In addition, the expression levels of IL-7 and IL-7R correlated well with that of VEGF-D, lymphatic vessels density (LVD), clinical stages, lymph node metastasis, and poor prognosis in 100 human non-small cell lung cancer (NSCLC) specimens analysed. Taken together, our results provide evidence that IL-7/IL-7R induce VEGF-D up-regulation and promote lymphangiogenesis via c-Fos/c-Jun pathway in lung cancer.
Ming
Jian
J
Department of Pathology, College of Basic Medical Sciences, China Medical University, Heping District, Shenyang, Liaoning, China.
Zhang
Qingfu
Q
Qiu
Xueshan
X
Wang
Enhua
E
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D016019:Survival Analysis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; D015851:Interleukin-7; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D042643:Vascular Endothelial Growth Factor D