Abstract
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.
MeSH terms
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Aged
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Carcinoma, Non-Small-Cell Lung / physiopathology
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DNA-Binding Proteins / metabolism
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Female
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Humans
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Interleukin-7 / pharmacology
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Interleukin-7 / physiology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lung Neoplasms / physiopathology*
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Lymphangiogenesis / physiology*
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Staging
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-jun / physiology*
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RNA, Messenger / genetics
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RNA, Neoplasm / genetics
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Receptors, Interleukin-7 / physiology
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Recombinant Proteins / pharmacology
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Survival Analysis
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Transcription Factor AP-1 / metabolism
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Tumor Cells, Cultured
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Up-Regulation / drug effects
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Up-Regulation / physiology
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Vascular Endothelial Growth Factor D / biosynthesis*
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Vascular Endothelial Growth Factor D / genetics
Substances
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DNA-Binding Proteins
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Interleukin-7
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Neoplasm Proteins
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Interleukin-7
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Recombinant Proteins
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Transcription Factor AP-1
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Vascular Endothelial Growth Factor D