Abstract
Fibroblast growth factor binding protein 1 (FGFBP1) is expressed in various tumors and may serve as a diagnostic marker and/or a therapeutic target. Previous studies suggested FGFBP1 functions as an angiogenic switch molecule by regulating the activity of FGF2, and it was later found to associate with a broad spectrum of FGFs. To study FGFBP1, we used zebrafish, in which the function of extracellular matrix protein can be easily studied in intact tissues or organisms. When Fgfbp1 expression was knocked down, morphants manifested massive cell death and structural abnormalities. Cell death was most prominent in the brain and the neural tube, but not limited to those regions. These findings suggest that the primary function of Fgfbp1 may be to sustain cellular survival throughout embryogenesis. For comparison, the expression of fgf2 was limited to the early stage of embryogenesis and fgf2 morphants showed more severe phenotype, with high morbidity before reaching 14-somites. Taken together, our work reveals the physiologic function of Fgfbp1, and that its function could be exerted in a Fgf2-independent manner.
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Abuharbeid, S., Czubayko, F., and Aigner, A. (2006). The fibroblast growth factor-binding protein FGF-BP. Int. J. Biochem. Cell Biol. 38, 1463–1468.
Aigner, A., Butscheid, M., Kunkel, P., Krause, E., Lamszus, K., Wellstein, A., and Czubayko, F. (2001). An FGF-binding protein (FGF-BP) exerts its biological function by parallel paracrine stimulation of tumor cell and endothelial cell proliferation through FGF-2 release. Int. J. Cancer 92, 510–517.
Aviles, R.J., Annex, B.H., and Lederman, R.J. (2003). Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF-2). Br. J. Pharmacol. 140, 637–646.
Beer, H.D., Bittner, M., Niklaus, G., Munding, C., Max, N., Goppelt, A., and Werner, S. (2005). The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair. Oncogene 24, 5269–5277.
Chan, J., Bayliss, P.E., Wood, J.M., and Roberts, T.M. (2002). Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell 1, 257–267.
Czubayko, F., Smith, R.V., Chung, H.C., and Wellstein, A. (1994). Tumor growth and angiogenesis induced by a secreted binding protein for fibroblast growth factors. J. Biol. Chem. 269, 28243–28248.
Czubayko, F., Liaudet-Coopman, E.D., Aigner, A., Tuveson, A.T., Berchem, G.J., and Wellstein, A. (1997). A secreted FGFbinding protein can serve as the angiogenic switch in human cancer. Nat. Med. 3, 1137–1140.
Damon, D.H., Lobb, R.R., D’Amore, P.A., and Wagner, J.A. (1989). Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biological half-life. J. Cell Physiol. 138, 221–226.
Dono, R., Texido, G., Dussel, R., Ehmke, H., and Zeller, R. (1998). Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO J. 17, 4213–4225.
Eisenmann, K.M., VanBrocklin, M.W., Staffend, N.A., Kitchen, S.M., and Koo, H.M. (2003). Mitogen-activated protein kinase pathway-dependent tumor-specific survival signaling in melanoma cells through inactivation of the proapoptotic protein bad. Cancer Res. 63, 8330–8337.
Eswarakumar, V.P., Lax, I., and Schlessinger, J. (2005). Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 16, 139–149.
Grant, S., Qiao, L., and Dent, P. (2002). Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival. Front Biosci. 7, d376–389.
Harada, H., Quearry, B., Ruiz-Vela, A., and Korsmeyer, S.J. (2004). Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc. Natl. Acad. Sci. USA 101, 15313–15317.
Hauptmann, G., and Gerster, T. (1994). Two-color whole-mount in situ hybridization to vertebrate and Drosophila embryos. Trends Genet 10, 266.
Kagan, B.L., Henke, R.T., Cabal-Manzano, R., Stoica, G.E., Nguyen, Q., Wellstein, A., and Riegel, A.T. (2003). Complex regulation of the fibroblast growth factor-binding protein in MDA-MB-468 breast cancer cells by CCAAT/enhancer-binding protein beta. Cancer Res. 63, 1696–1705.
Korc, M., and Friesel, R.E. (2009). The role of fibroblast growth factors in tumor growth. Curr. Cancer Drug Targets 9, 639–651.
Kurtz, A., Wang, H.L., Darwiche, N., Harris, V., and Wellstein, A. (1997). Expression of a binding protein for FGF is associated with epithelial development and skin carcinogenesis. Oncogene 14, 2671–2681.
Lawson, N.D., and Weinstein, B.M. (2002). In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev. Biol. 248, 307–318.
Ley, R., Balmanno, K., Hadfield, K., Weston, C., and Cook, S.J. (2003). Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim. J. Biol. Chem. 278, 18811–18816.
Ortega, S., Ittmann, M., Tsang, S.H., Ehrlich, M., and Basilico, C. (1998). Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2. Proc. Natl. Acad. Sci. USA 95, 5672–5677.
Panka, D.J., Atkins, M.B., and Mier, J.W. (2006). Targeting the mitogen-activated protein kinase pathway in the treatment of malignant melanoma. Clin. Cancer Res. 12, 2371s–2375s.
Presta, M., Dell’Era, P., Mitola, S., Moroni, E., Ronca, R., and Rusnati, M. (2005). Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 16, 159–178.
Ray, R., Cabal-Manzano, R., Moser, A.R., Waldman, T., Zipper, L.M., Aigner, A., Byers, S.W., Riegel, A.T., and Wellstein, A. (2003). Up-regulation of fibroblast growth factor-binding protein, by beta-catenin during colon carcinogenesis. Cancer Res. 63, 8085–8089.
Sommer, A., and Rifkin, D.B. (1989). Interaction of heparin with human basic fibroblast growth factor: protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan. J. Cell Physiol. 138, 215–220.
Tassi, E., Al-Attar, A., Aigner, A., Swift, M.R., McDonnell, K., Karavanov, A., and Wellstein, A. (2001). Enhancement of fibroblast growth factor (FGF) activity by an FGF-binding protein. J. Biol. Chem. 276, 40247–40253.
Vaccarino, F.M., Schwartz, M.L., Raballo, R., Nilsen, J., Rhee, J., Zhou, M., Doetschman, T., Coffin, J.D., Wyland, J.J., and Hung, Y.T. (1999). Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat. Neurosci. 2, 246–253.
Wang, X.C., Chen, J.H., Crab, J.W., and Sato, J.D. (1998). Purifica tion of heparin-binding protein HBp17 and identification of HBp17 heparin binding site. Biochem. Mol. Biol. Int. 46, 81–87.
Wu, D.Q., Kan, M.K., Sato, G.H., Okamoto, T., and Sato, J.D. (1991). Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors. J. Biol. Chem. 266, 16778–16785.
Xie, B., Tassi, E., Swift, M.R., McDonnell, K., Bowden, E.T., Wang, S., Ueda, Y., Tomita, Y., Riegel, A.T., and Wellstein, A. (2006). Identification of the fibroblast growth factor (FGF)-interacting domain in a secreted FGF-binding protein by phage display. J. Biol. Chem. 281, 1137–1144.
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Lee, Ho., Choe, H., Seo, K. et al. Fgfbp1 is essential for the cellular survival during zebrafish embryogenesis. Mol Cells 29, 501–507 (2010). https://doi.org/10.1007/s10059-010-0062-7
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DOI: https://doi.org/10.1007/s10059-010-0062-7