Fibroblast Growth Factors In Development Research Articles

The FGF-2-Derived Peptide FREG Inhibits Melanoma Growth In Vitro and In Vivo

Previous data report that fibroblast growth factor-2 (FGF-2)-derived peptide FREG potently inhibits FGF-2-dependent angiogenesis in vitro and in vivo. Here, we show that FREG inhibits up to 70% in vitro growth and invasion/migration of smooth muscle and melanoma cells. Such inhibition is mediated by platelet-derived growth factor-receptor-α (PDGF-Rα); in fact, proliferation and migration were restored upon PDGF-Rα neutralization. Further experiments demonstrated that FREG interacts with PDGF-Rα both in vitro and in vivo and stimulates its phosphorylation. We have previously shown that overexpressing PDGF-Rα strongly inhibits melanoma growth in vivo; we, therefore, hypothesized that PDGF-Rα agonists may represent a novel tool to inhibit melanoma growth in vivo. To support this hypothesis, FREG was inoculated intravenously (i.v.) in a mouse melanoma model and markedly inhibited pulmonary metastases formation. Immunohistochemical analyses showed less proliferation, less angiogenesis, and more apoptosis in metastasized lungs upon FREG treatment, as compared to untreated controls. Finally, in preliminary acute toxicity studies, FREG showed no toxicity signs in healthy animals, and neither microscopic nor macroscopic toxicity at the liver, kidney, and lungs level. Altogether, these data indicate that FREG systemic treatment strongly inhibits melanoma metastases development and indicate for the first time that agonists of PDGF-Rα may control melanoma both in vitro and in vivo.

Fibroblast Growth Factors in Development and Cancer: Insights from the Mammary and Prostate Glands

The fibroblast growth factor (FGF) family is comprised of 22 ligands that bind and activate several FGF receptor (FGFR) isoforms. Critical roles for FGFs and FGFRs have been well-established during embryonic development. For example, the FGF10/FGFR2IIIb axis has been linked to embryonic development of both the mammary and prostate glands, which are the subject of this review. Furthermore, recent studies using novel mouse models have suggested that this pathway also participates in postnatal development in the mammary and prostate glands. These studies have provided novel insights into the mechanisms by which FGFs and FGFRs promote ductal outgrowth and branching morphogenesis. In addition to the established roles of FGFs in development, aberrant activation of the FGF pathway has been linked to tumor progression in both breast and prostate cancer. Recent studies have linked FGFR1 expression and single nucleotide polymorphisms in FGFR2 to breast cancer. Furthermore, novel pre-clinical models have demonstrated the ability of FGFRs to promote numerous aspects of breast and prostate cancer. Understanding the roles of FGFs in development will provide insights into the mechanisms by which deregulation of the FGF pathway leads to tumorigenesis, ultimately leading to the development of novel therapeutic strategies designed to target this pathway in cancer patients.

Distribution of basic fibroblast growth factor in the developing rat brain

Previous studies in vitro indicate that basic fibroblast growth factor participates in the survival, proliferation and differentiation of immature neurol cells, predicting that it may have the same types of roles in vivo. In order to evaluate a possible role of basic fibroblast growth factor in neurol development, we have examined its localization in the rodent brain at critical stages of development. We characterized basic fibroblast growth factor immunoreactivity at embryonic days 13 and 18, and postnatal days 1, 4, 6, 10, 20 and 90. Our results showed that basic fibroblast growth factor was transiently expressed by different cellular phenotypes throughout development. At embryonic day 13, basic fibroblast growth factor immunoreactivity was sparsely distributed in various cell phenotypes. At embryonic day 18, the primitive cerebral cortex showed basic fibroblast growth factor immunoreactivity within its emerging laminar structure, including the cortical plate and subplate regions. At postnatal day 1, basic fibroblast growth factor immunoreactivity was mostly concentrated in the hippocampal subfields cornu Ammon 1, cornu Ammon 2 and cornu Ammon 3, and neurons of the medical septum and the vertical limb of the diagonal band nuclei. At postnatal days 4–6, astrocyte-like cells showed basic fibroblast growth factor immunoreactivity for the first time during development. At this stage, basic fibroblast growth factor in the hippocampus was mostly shown within subfields cornu Ammon 2 and cornu Ammon 1. In the medical septum, just a few neuronal profiles were weakly stained, and basic fibroblast growth factor positive astrocytes appeared to accumulate around these basic fibroblast growth factor-stained neurons. At postnatal day 20, the adult pattern of basic fibroblast growth factor immunoreactivity was fully established. Astrocytes throughout the brain expressed basic fibroblast growth factor, and neuronal basic fibroblast growth factor was restricted to particular populations such as cingulate cortex and hippocampus. The cornu Ammon 2 subfield was the main neuronal location for basic fibroblast growth factor in the mature hippocampus. Our results showed that the cellular location of basic fibroblast growth factor changes during development, suggesting that basic fibroblast growth factor has multiple and evolving roles during histogenesis and differentiation of the CNS.

Basic fibroblast growth factor in development and after isoproterenol-induced injury in the rat heart

Basic fibroblast growth factor in development and after isoproterenol-induced injury in the rat heart