Aging
Navigate
Submit an Article
Research Paper|Volume 11, Issue 23|pp 11040—11053

Sphingosine-1-phosphate promotes PDGF-dependent endothelial progenitor cell angiogenesis in human chondrosarcoma cells

Chao-Qun Wang1, Chih-Yang Lin2, Yuan-Li Huang3, Shih-Wei Wang2,4, Yan Wang5, Bi-Fei Huang1, Yu-Wei Lai6,7, Shun-Long Weng8, Yi-Chin Fong9,10, Chih-Hsin Tang3,11,12, Zhong Lv13
  • 1Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
  • 2Department of Medicine, Mackay Medical College, New Taipei, Taiwan
  • 3Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
  • 4Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 5Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
  • 6Division of Urology, Taipei Hospital Renai Branch, Taipei, Taiwan
  • 7Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan
  • 8Department of Obstetrics and Gynaecology, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan
  • 9Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
  • 10Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
  • 11Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
  • 12Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
  • 13Department of General Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
* Equal contribution
Received: August 15, 2019Accepted: November 18, 2019Published: December 6, 2019
https://doi.org/10.18632/aging.102508

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.