Study the role of bFGF in VEGF expression and angiogenesis in human chondrosarcoma cells

Autor: Kai-Wei Lin, 林楷為
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Chondrosarcoma is the common malignant tumor which developed in bone. An effective adjuvant therapy remains inadequate for treatment and poor prognosis in chondorsarcoma, therefore, it is important to explore a novel and adequate remedy. Angiogenic switch is rate-limiting steps in tumor progression which explains the biological process of neovessel formation in tumor microenvironment and gets the blood supply. Enormous studies indicate that endothelial progenitor cells (EPCs) promote angiogenic switch and contribute to tumor angiogenesis-related growth. Basic fibroblast growth factor (bFGF) is a secrete cytokine that regulates biological activities including angiogenic switch, and expression of bFGF correlates with tumorigenesis. However, the role of bFGF in angiogenic switch by affecting EPCs within human chondrosarcoma microenvironment is poorly discussed. Here, we found that bFGF inducedVEGF expression through FGFR1/c-Src/p38/NF-κB signaling pathway in chondrosarcoma. Moreover, the bFGF-induced VEGF expression in chondrosarcoma recruited EPCs, resulting angiogenic switch in tumor microenvironment. Our in vivo data revealed that tumor-secreted bFGF promoted angiogenesis in the chick chorioallantoic membrane assay (CAM) and mouse plug assay. As the consequence of bFGF-regulated angiogenic switch, the xenograft mouse model data showed that bFGF regulated angiogenesis-associated tumor growth in chondrosarcoma. Finally, the bFGF was found to be highly expressed in chondrosarcoma patients than normal cartilage, and bFGF expression was positively correlated with VEGF expression and tumor stage in chondrosarcoma specimens. The present study will provide the opportunity to develop a novel therapeutic target for chondrosarcoma progression.
Databáze: Networked Digital Library of Theses & Dissertations
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