Social defeat stress promotes tumor growth and angiogenesis by upregulating vascular endothelial growth factor/extracellular signal-regulated kinase/matrix metalloproteinase signaling in a mouse model of lung carcinoma
| Autor: | Yi‑Jie Du, Jing‑Feng Wu, Baojun Liu, Jingcheng Dong, Changqing Xu, Xiao‑Hong Duan, Hai‑Lin Xu, Jing‑Jing Le, Shumeng Ji, Xiao Wu, Xiao‑Fang You, Bei Li |
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| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Cancer Research Angiogenesis Carcinogenesis MAP Kinase Signaling System Neural Cell Adhesion Molecule L1 Biology Biochemistry chemistry.chemical_compound Carcinoma Lewis Lung Mice Genetics medicine Animals Phosphorylation Lung cancer Autocrine signalling Molecular Biology Oncogene Lewis lung carcinoma medicine.disease Vascular Endothelial Growth Factor Receptor-2 Vascular endothelial growth factor Gene Expression Regulation Neoplastic Vascular endothelial growth factor A Oncology Vascular endothelial growth factor C chemistry Matrix Metalloproteinase 9 Cancer research Molecular Medicine Matrix Metalloproteinase 2 Stress Psychological Signal Transduction |
| Zdroj: | Molecular medicine reports. 12(1) |
| ISSN: | 1791-3004 |
| Popis: | Numerous epidemiological and experimental animal studies have indicated that chronic psychological stress may promote tumor development. However, the underlying molecular mechanisms by which chronic stress promotes tumorigenesis remain to be fully elucidated and animal models have not yet been well established. In the present study, an established mouse model of repeated social defeat stress (RSDS), was generated and used to investigate the effect of stress on tumor growth and metastasis. C57BL/6 mice were exposed to RSDS for 10 days, followed by subcutaneousl inoculation with Lewis lung carcinoma cells for seven days. The tumor weight and volume as well as the number of the lung metastatic nodules were then determined. Vascular endothelial growth factor (VEGF) serum levels were measured using ELISAs. In addition, expression levels of VEGF receptor (VEGFR) and L1 cell adhesion molecule (L1CAM) messenger (m)RNA were confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, protein expression levels of phosphorlyated extracellular signal-regulated kinase (pERK), matrix metalloproteinase (MMP)-2 and MMP-9 were examined using western blot analysis. The results showed that RSDS significantly increased the weight and the volume of the primary tumor as well as the number of the lung metastatic nodules. Serum VEGF levels were significantly higher in the tumor-stress group compared with those of the unstressed tumor mice. In addition, tumors in stressed animals demonstrated markedly enhanced expression of VEGFR-2 and L1CAM mRNA as well as pERK, MMP-2 and MMP-9 protein expression. In conclusion, these results suggested that RSDS contributed to lung cancer progression, angiogenesis and metastasis, which was partially associated with increased VEGF secretion and therefore the activation of the ERK signaling pathway, resulting in the induction of MMP-2 and MMP-9 protein expression. |
| Databáze: | OpenAIRE |
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