CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells

Guan Ting Liu, Yuan Li Huang, Huey En Tzeng, Chun Hao Tsai, Shih Wei Wang, Chih Hsin Tang

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been shown to facilitate tumor progression and metastasis. However, the relationship of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. MicroRNA analysis was performed in CCL5-treated chondrosarcoma cells versus control cells to investigate the mechanism of CCL5-mediated promotion of chondrosarcoma angiogenesis. Among the miRNAs regulated by CCL5, miR-199a was the most downregulated miRNA after CCL5 treatment. In addition, co-transfection with miR-199a mimic reversed the CCL5-mediated VEGF expression and angiogenesis in vitro and in vivo. Moreover, overexpression of CCL5 increased tumor-associated angiogenesis and tumor growth by downregulating miR-199a in the xenograft tumor angiogenesis model. Taken together, these results demonstrated that CCL5 promotes VEGF-dependent angiogenesis in human chondrosarcoma cells by downregulating miR-199a.

Original languageEnglish
Pages (from-to)476-487
Number of pages12
JournalCancer Letters
Volume357
Issue number2
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • Angiogenesis
  • CCL5
  • Chondrosarcoma
  • MiR-199a
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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