Research Paper Volume 11, Issue 21 pp 9767—9777
Resistin enhances angiogenesis in osteosarcoma via the MAPK signaling pathway
- 1 Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
- 2 Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan
- 3 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
- 4 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 5 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- 6 Division of Colon and Rectal Surgery, Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan
- 7 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 8 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 9 School of Medicine, China Medical University, Taichung, Taiwan
- 10 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
received: August 2, 2019 ; accepted: October 28, 2019 ; published: November 13, 2019 ;https://doi.org/10.18632/aging.102423
How to Cite
Copyright © 2019 Tsai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.