Resistin enhances angiogenesis in osteosarcoma via the MAPK signaling pathway
| Autor: | Chien-Kuo Han, Yuan-Li Huang, Shih-Ping Cheng, Cheng-Ta Lai, Shih-Wei Wang, Jie-Jen Lee, Yi-Chin Fong, Chih-Hsin Tang, Hsiao-Chi Tsai |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
MAPK/ERK pathway
Vascular Endothelial Growth Factor A Aging endocrine system diseases Angiogenesis MAP Kinase Signaling System Drug Evaluation Preclinical Adipokine Chick Embryo Endothelial progenitor cell VEGF-A angiogenesis Cell Line Tumor medicine Animals Humans Resistin Tube formation Osteosarcoma Neovascularization Pathologic Chemistry NF-kappa B nutritional and metabolic diseases Cell Biology medicine.disease MAPK Cancer research Signal transduction hormones hormone substitutes and hormone antagonists Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Over the last two decades, there have been no significant changes in patient outcomes in relation to the treatment of osteosarcoma, an aggressive malignant neoplasm. It is known that vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and in osteosarcoma. Moreover, VEGF-A expression correlates with clinical stages of osteosarcoma. The adipokine resistin exhibits proinflammatory, proangiogenic and metastatic properties, and evidence suggests that resistin may serve as a prognostic biomarker linking obesity and inflammation to cancer. However, whether resistin has a role in osteosarcoma angiogenesis is unclear. This investigation shows that resistin promotes VEGF-A expression in human osteosarcoma cells and activates the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 signaling pathways, while ERK, JNK, and p38 inhibitors or their small interfering RNAs (siRNAs) inhibit resistin-induced VEGF-A expression as well as endothelial progenitor cell (EPC) migration and tube formation. We also found that resistin upregulates VEGF-A expression by enhancing activation of the transcription factor nuclear factor-kappa B (NF-κB). Finally, resistin promotes angiogenesis in the chick chorioallantoic membrane (CAM) model. Resistin appears to be a promising target for human osteosarcoma. |
| Databáze: | OpenAIRE |
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