Chondrosarcoma is the second most common primary malignant
bone cancer, with potential for local invasion and distant
metastasis.
Chemokine CCL5 (formerly
RANTES) of the
CC-chemokine family plays a crucial role in
metastasis. Angiogenesis is essential for the
cancer metastasis. However, correlation of CCL5 with
vascular endothelial growth factor (
VEGF) expression and angiogenesis in human
chondrosarcoma is still unknown. CCL5-mediated
VEGF expression was assessed by qPCR, ELISA, and Western blotting. CCL5-induced angiogenesis was examined by migration and tube formation in endothelial progenitor cells in vitro. CCL5 increased
VEGF expression and also promoted
chondrosarcoma conditional medium-mediated angiogenesis in vitro and in vivo. Stimulation of
chondrosarcoma with CCL5 augmented PI3K and Akt phosphorylation, while PI3K and Akt inhibitor or
siRNA abolished CCL5-induced
VEGF expression and angiogenesis. We also demonstrated CCL5 inhibiting miR-200b expression and miR-200b mimic reversing the CCL5-enhanced
VEGF expression and angiogenesis. Moreover, in
chondrosarcoma patients showed the positive correlation between CCL5 and
VEGF; negative correlation between CCL5 and miR-200b. Taken together, results demonstrate CCL5 promoting
VEGF-dependent angiogenesis in human
chondrosarcoma cells by down-regulating miR-200b through PI3K/Akt signaling pathway.