Tissue factor regulates tumor angiogenesis of retinoblastoma via the extracellular signal-regulated kinase pathway

Song,Hyun  Beom; Park,Kyung  Duk; Kim,Jin  Hyoung; Kim,Dong  Hun; Yu,Young   Suk; Kim,Jeong  Hun

doi:10.3892/or.2012.2048

Tissue factor regulates tumor angiogenesis of retinoblastoma via the extracellular signal-regulated kinase pathway

Authors:
- Hyun Beom Song
- Kyung Duk Park
- Jin Hyoung Kim
- Dong Hun Kim
- Young Suk Yu
- Jeong Hun Kim
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Affiliations: Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea, Department of Pediatrics, College of Medicine, Seoul National University, Seoul, Republic of Korea, Department of Radiology, College of Medicine, Chosun University, Gwangju, Republic of Korea
Published online on: September 20, 2012 https://doi.org/10.3892/or.2012.2048
Pages: 2057-2062

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Abstract

Retinoblastoma, a well-vascularized tumor that is dependent on a very robust angiogenic response, is the most common intraocular malignancy in children. Tissue factor (TF) is known to regulate tumor progression and in the present study we demonstrated that TF regulates tumor angiogenesis of retinoblastoma. In an orthotopic transplantation model of retinoblastoma, TF was selectively expressed in the proliferative area of retinoblastoma including tumor vessels as well as tumor cells, where TF expression was co-localized with endothelial cells of tumor vessels. TF expression progressively increased with fibroblast growth factor-2 (FGF-2)-induced proliferation of human umbilical vein endothelial cells (HUVECs), which was effectively inhibited by blockade of the TF pathway by TF pathway inhibitor (TFPI). In addition, FGF-2-induced angiogenic processes of migration and tube formation of vascular endothelial cells were also effectively suppressed by TFPI, which would be mediated by inhibition of extracellular signal-regulated kinase activation. Therefore, further to our previous report that TF is involved in tumor cell proliferation of retinoblastoma, our current data suggest that blockade of the TF pathway by TFPI could effectively inhibit tumor growth by suppressing tumor cell proliferation and tumor angiogenesis at the same time.

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