Abstract
Purpose: :
To investigate whether tissue factor (TF) regulates fibroblast growth factor (FGF)-2-induced angiogenesis in retinoblastoma.
Methods: :
In an experimental model of retinoblastoma, immunofluorescence staining for TF and CD31 as an endothelial cell maker was performed. With treatment of FGF-2 (10 ng/ml), TF expression in human umbilical vein endothelial cells (HUVECs) was measured by Western blotting. To confirm the role of TF in tumor angiogenesis in retinoblastoma, anti-angiogenic activity of TF pathway inhibitor (TFPI) was evaluated by FGF-2-induced proliferation, migration and in vitro tube formation assay of HUVECs. In addition, inhibition of ERK-1/2 phosphorylation by TFPI was measured by Western blot analysis.
Results: :
TF was highly expressed on vascular endothelial cells of retinoblastoma, co-localized with CD31. With FGF-2-induced proliferation of HUVECs, TF expression was significantly up-regulated. Interestingly, TFPI effectively blocked FGF-2-induced proliferation, migration and in vitro tube formation of HUVECs, which was accompanied by inhibition of ERK-1/2 phosphorylation.
Conclusions: :
Our results suggest that TF on tumor vessels of retinoblastoma could be involved in regulation of FGF-2 induced angiogenesis, which was mediated by ERK pathway.
Keywords: retinoblastoma • tumors • growth factors/growth factor receptors