Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis

Abstract

Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.

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

“…Our previous study indicated that bFGF is associated with chondrosarcoma progression and angiogenesis [23]. We have also previously reported finding a higher expression of bFGF in chondrosarcoma patients compared with normal cartilage [23].…”

“…We have also previously reported finding a higher expression of bFGF in chondrosarcoma patients compared with normal cartilage [23]. To examine the role of bFGF in the lymphangiogenesis of chondrosarcoma, we analyzed the VEGF-C expression profile in specimens from patients with chondrosarcomas.…”

“…Expression of bFGF is associated with tumor recurrence and reduced survival after surgical resection of oesophageal cancer [22]. In chondrosarcoma, we have previously reported that bFGF increases VEGF-A expression and subsequently promotes endothelial progenitor cell-primed angiogenesis [23], implying that bFGF is involved in the metastatic process of chondrosarcoma.…”

CCN1 Promotes VEGF Production in Osteoblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-126 Expression in Rheumatoid Arthritis

“…(11,12) Recruited endothelial progenitor cells (EPCs) from the bone marrow migrate to and differentiate into mature endothelial cells at the relevant sites of inflammation, where the cells are incorporated into blood vessel repair and neovascularization. (13) VEGF not only promotes angiogenesis by inducing proliferation, migration and capillary-like tube formation of EPCs (14,15) ; accumulating evidence reveals that VEGF is regulated by microRNAs (miRNAs) at multiple levels during angiogenesis. (16,17) These miRNAs are small, noncoding RNA molecules that control gene expression, map to introns of protein-coding genes, and function as key posttranscriptional regulators of gene expression and RNA silencing.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…FGF plays a role in the migration and proliferation of endothelial cells along with the proliferation of smooth muscle cells and fibroblasts. Basic FGF (bFGF), a secreted cytokine, regulates angiogenesis through induction of VEGF expression via the FGFR1/c-Src/p38/NF-kB (nuclear factor kB) signaling pathway, triggering angiogenesis of endothelial progenitor cells (Tzeng et al 2015). Platelet derived growth factor (PDGF) is critical for pericyte recruitment and maturation of neovascular vessels (Alvarez et al 2006).…”