Basic fibroblast growth factor promotes VEGF-C-dependent lymphangiogenesis via inhibition of miR-381 in human chondrosarcoma cells

Huey En Tzeng, An Chen Chang, Chun Hao Tsai, Shih Wei Wang, Chih Hsin Tang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A chondrosarcoma is a common, primary malignant bone tumor that can grow to destroy the bone, produce fractures and develop soft tissue masses. Left untreated, chondrosarcomas metastasize through the vascular system to the lungs and ultimately lead to large metastatic deposits of the malignant cartilage taking over lung volume and function. Vascular endothelial growth factor (VEGF)-C has been implicated in tumor-induced lymphangiogenesis and elevated expression of VEGF-C has been found to correlate with cancer metastasis. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis and metastasis. We have previously reported on the important role of bFGF in angiogenesis in chondrosarcomas. However, the effect of bFGF in VEGF-C regulation and lymphangiogenesis in chondrosarcomas is poorly understood. In this investigation, we demonstrate a correlation exists between bFGF and VEGF-C in tissue specimens from patients with chondrosarcomas. To examine the lymphangiogenic effect of bFGF, we used human lymphatic endothelial cells (LECs) to mimic lymphatic vessel formation. We found that bFGF-treated chondrosarcomas promoted LEC tube formation and cell migration. In addition, bFGF knockdown inhibited lymphangiogenesis in vitro and in vivo. We also found that bFGF-induced VEGF-C is mediated by the platelet-derived growth factor receptor (PDGFR) and c-Src signaling pathway. Furthermore, bFGF inhibited microRNA-381 expression via the PDGFR and c-Src cascade. Our study is the first to describe the mechanism of bFGF-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. Thus, bFGF could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

Original languageEnglish
Pages (from-to)38566-38578
Number of pages13
JournalOncotarget
Volume7
Issue number25
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

Lymphangiogenesis
Vascular Endothelial Growth Factor C
Chondrosarcoma
Fibroblast Growth Factor 2
Platelet-Derived Growth Factor Receptors
Neoplasm Metastasis
human MIRN381 microRNA
Endothelial Cells
Neoplasms
Lung
Lymphatic Vessels
Bone Fractures
MicroRNAs
Cartilage
Cell Movement
Blood Vessels

Keywords

  • BFGF
  • Chondrosarcoma
  • Lymphangiogenesis
  • MiR-381
  • VEGF-C

ASJC Scopus subject areas

  • Oncology

Cite this

Basic fibroblast growth factor promotes VEGF-C-dependent lymphangiogenesis via inhibition of miR-381 in human chondrosarcoma cells. / Tzeng, Huey En; Chang, An Chen; Tsai, Chun Hao; Wang, Shih Wei; Tang, Chih Hsin.

In: Oncotarget, Vol. 7, No. 25, 01.01.2016, p. 38566-38578.

Research output: Contribution to journalArticle

Tzeng, Huey En ; Chang, An Chen ; Tsai, Chun Hao ; Wang, Shih Wei ; Tang, Chih Hsin. / Basic fibroblast growth factor promotes VEGF-C-dependent lymphangiogenesis via inhibition of miR-381 in human chondrosarcoma cells. In: Oncotarget. 2016 ; Vol. 7, No. 25. pp. 38566-38578.
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