Research Paper Volume 11, Issue 23 pp 11040—11053
Sphingosine-1-phosphate promotes PDGF-dependent endothelial progenitor cell angiogenesis in human chondrosarcoma cells
- 1 Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
- 2 Department of Medicine, Mackay Medical College, New Taipei, Taiwan
- 3 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 4 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
- 5 Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
- 6 Division of Urology, Taipei Hospital Renai Branch, Taipei, Taiwan
- 7 Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- 8 Department of Obstetrics and Gynaecology, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan
- 9 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 10 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 11 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- 12 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 13 Department of General Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
Received: August 15, 2019 Accepted: November 18, 2019 Published: December 6, 2019
https://doi.org/10.18632/aging.102508How to Cite
Copyright © 2019 Wang 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.
Abstract
The malignant bone tumors that are categorized as chondrosarcomas display a high potential for metastasis in late-stage disease. Higher-grade chondrosarcomas contain higher levels of expression of platelet-derived growth factor (PDGF) and its receptor. The phosphorylation of sphingosine by sphingosine kinase enzymes SphK1 and SphK2 generates sphingosine-1-phosphate (S1P), which inhibits human chondrosarcoma cell migration, while SphK1 overexpression suppresses lung metastasis of chondrosarcoma. We sought to determine whether S1P mediates levels of PDGF-A expression and angiogenesis in chondrosarcoma. Surprisingly, our investigations found that treatment of chondrosarcoma cells with S1P and transfecting them with SphK1 cDNA increased PDGF-A expression and induced angiogenesis of endothelial progenitor cells (EPCs). Ras, Raf, MEK, ERK and AP-1 inhibitors and their small interfering RNAs (siRNAs) inhibited S1P-induced PDGF-A expression and EPC angiogenesis. Our results indicate that S1P promotes the expression of PDGF-A in chondrosarcoma via the Ras/Raf/MEK/ERK/AP-1 signaling cascade and stimulates EPC angiogenesis.