Interleukin 7 and its receptor promote cell proliferation and induce lymphangiogenesis in non-small cell lung cancer.
- Author:
Jian MING
1
;
Qing-fu ZHANG
;
Yan-duo JIANG
;
Guo-cheng JIANG
;
Xue-shan QIU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Carcinoma, Non-Small-Cell Lung; metabolism; pathology; Cell Line, Tumor; Cell Proliferation; Cyclin D1; metabolism; Female; Humans; Interleukin-7; metabolism; physiology; Lung Neoplasms; metabolism; pathology; Lymphangiogenesis; Lymphatic Metastasis; Male; Mice; Mice, Nude; Middle Aged; Neoplasm Staging; Neoplasm Transplantation; Proto-Oncogene Proteins c-fos; metabolism; Proto-Oncogene Proteins c-jun; metabolism; Receptors, Interleukin-7; metabolism; physiology; Vascular Endothelial Growth Factor D; metabolism
- From: Chinese Journal of Pathology 2012;41(8):511-518
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro.
METHODSImmunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors.
RESULTSIL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors.
CONCLUSIONSIL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.
