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A secreted FGF-binding protein can serve as the angiogenic switch in human cancer

Abstract

The growth and metastatic spread of cancer is directly related to tumor angiogenesis1, and the driving factors need to be understood to exploit this process therapeutically2,3. However, tumor cells and their normal stroma express a multitude of candidate angiogenic factors2, and very few specific inhibitors have been generated to assess which of these gene products are only innocent bystanders and which contribute significantly to tumor angiogenesis4–6 and metastasis6–8. Here we investigated whether the expression in tumors of a secreted fibroblast growth factor (FGF)-binding protein (FGF-BP)9 that mobilizes and activates10 locally stored FGFs (ref. 11) can serve as an angiogenic switch molecule3. Developmental expression of the retinoid-regulated FGf-BP gene12 is prominent in the skin and intestine during the perinatal phase and is down-modulated in the adult13. The gene is, however, upregulated in carcinogen-induced skin tumors13, in squamous cell carcinoma (SCC)10 and in some colon cancer cell lines and tumor samples. To assess the significance of FGF-BP expression in tumors, we depleted human SCC (ME-180) and colon carcinoma (LS174T) cell lines of their endogenous FGF-BP by targeting with specific ribozymes. We found that the reduction of FGF-BP reduced the release of biologically active basic FGF (bFGF) from cells in culture. Furthermore, the growth and angiogenesis of xenograft tumors in mice was decreased in parallel with the reduction of FGF-BP. This suggests that human tumors can utilize FGF-BP as an angiogenic switch molecule.

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Czubayko, F., Liaudet-Coopman, E., Aigner, A. et al. A secreted FGF-binding protein can serve as the angiogenic switch in human cancer. Nat Med 3, 1137–1140 (1997). https://doi.org/10.1038/nm1097-1137

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