FGF, basic

Basic FGF can also stimulate murine hemopoietic progenitors in vitro. It is synergistic with hemopoietic growth factors such as GM-CSF, EPO, and Meg-CSF and has radioprotective activity in vivo, increasing the number of day-9 and day-12 CFU-S from lethaUy irradiated animals (195). Furthermore, b-FGF combiaed with GM-CSF protects against the killing of murine and human CFU-GM exposed to radiation in vitro (195). 

Fig. 4 Interaction of basic FGF on heparan sulfate PG (1) and free GAG (2) induces FGFR dimerization, leading to tyrosine kinase (TK) activation and signal transduction.

The means by which FGFs are secreted from their producer cells remains to be fully elucidated. Several (e.g. FGF-1 and FGF-2, also known as acidic-FGF and basic-FGF, respectively Figure 7.4) do not contain a classical signal sequence for secretion (i.e. a short N-terminus stretch of hydrophobic amino acid residues which direct newly synthesized polypeptides to the endoplasmic reticulum and hence ultimately facilitates their extracellular release). Interestingly, several such FGFs display a nucleas localization motif and have been... 

Sellke FW, Wang SY Friedman M, et al. Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation. Am J Physiol I 994 267(4 Pt 2) H1303-H13 I I. 

FGF receptor isoforms, FGFRl, FGFR2, and FGFR3, form both homodimeric and heterodimeric receptor species. The multiplicity of FGF receptors explains the selective, individual responsiveness of cells and tissues to either acid or basic FGFs. 

Bashkin, P, Doctrow, S., Klagsbrun, M., Svahn, C. M., Folkman, J. and Vlo-davski, I. (1989). Basic FGF binds to subendothelial ECM and is released by heparitinase and heparin-like molecules. Biochemistry 28, 1737-1743. 

Mignatti, R, Morimoto, T. and Rifkin, D. B. (1991). Basic FGF released by single, isolated cells stimulates their migration in an autocrine manner. Proc. Natl. Acad. Sci. USA 88, 11007-11011. 

In addition to an apparently low thermal stability, FGF appears to face additional problems in maintaining its native, functional structure. Human aFGF contains three cysteine residues and the related basic FGF (bFGF) contains four cysteines. These residues are present in the active protein as free cysteine residues and oxidation, to form either inter- or intra-chain disulfide bonds, has been demonstrated to inactivate the protein... 

Mast cell neutral proteases have also been implicated in tissue remodelling. Canine tryptase induces proliferation of Chinese hamster and rat fibroblasts and also proten-tiates their respronse to basic FGF (Ruoss et al., 1991). 

Araujo, D. M. and Cotman, C. W., Basic FGF in astroglial, microglial, and neuronal cultures. Characterization of binding sites and modulation of release by lymphokines and trophic factors, J. Neurosci., 112, 1668, 1992. 

Nakahara, Y., Gage, F. H., and Tuszynski, M. H., Grafts of fibroblasts genetically modified to secrete NGF, BDNF, NT-3, or basic FGF elicit differential responses in the adult spinal cord, Cell Transplant., 5, 191, 1996. 

Emoto, N., Gonzalea, A.-M., Walicke, P. A., Wada, E., Simmons, D. M., Shimasaki, S., and Baird, A., Basic fibroblast growth factor (FGF) in the central nervous system identification of specific loci of basic FGF expression in the rat brain, Growth Factors, 2,21, 1989. 

Grothe, C., Zachmann, K., and Unsicker, K., Basic FGF-like immunoreactivity in the developing and adult rat brain stem, J. Comp. Neurol., 305, 328, 1991. 

Mattson, M. R, Tomaselli, K. J., and Rydel, R.E., Calcium-destabilizing and neuro-degenerative effects of aggregated beta-amyloid peptide are attenuated by basic FGF, Brain Res., 621, 35, 1993. 

Unsicker, K., Reichert-Preibsch, H., and Wewetzer, K., Stimulation of neuronal survival by basic FGF and CNTF is a direct effect and not mediated by non-neuronal cells evidence from single cell cultures, Dev. Brain Res., 65, 285, 1992. 

Otto, D. and Unsicker, K., Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice, J. Neurosci., 10, 1912, 1990. 

The progression and growth of ovarian carcinoma are also dependent on chemokine-mediated angiogenesis. In one study, the in vitro production of CXCL8 by five human ovarian cancer lines correlated with tumor neovascularization and cancer-related death when implanted into the peritoneum of immunocompromised mice, whereas VEGF production correlated only with ascites production after implantation, but basic FGF did not correlate with the outcome [70]. This concept was further substantiated in patients with ovarian cancer where ascites fluid angiogenic activity directly correlated to CXCL8 [71]. 

Stocker, K.M., Sherman, L., Rees, S. and Ciment, G. (1991) Basic FGF and TGF-beta 1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos. Development 111 635-645. 

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