Examining new models for the study of autocrine and paracrine mechanisms of angiogenesis through FGF2-transfected endothelial and tumour cells.
Angiogenesis is the process of generating new capillary blood vessels. Uncontrolled endothelial cell proliferation is observed in tumour neovascularization. Several growth factors and cytokines have been shown to stimulate endothelial cell proliferation in vitro and in vivo and among them FGF2 was one of the first to be characterised. FGF2 is a Mr 18,000 heparin-binding cationic polypeptide that induces proliferation, migration, and protease production in endothelial cells in culture and neovascularization in vivo. FGF2 interacts with endothelial cells through two distinct classes of receptors, the high affinity tyrosine-kinase receptors (FGFRs) and low affinity heparan sulfate proteoglycans (HSPGs) present on the cell surface and in the extracellular matrix. Besides experimental evidence for paracrine mode of action for FGF2, some observations raise the hypothesis that FGF2 may also play an autocrine role in endothelial cells. FGF2 may therefore represent a target for anti-angiogenic therapies. In order to assess the angiostatic potential of different classes of compounds, novel experimental models have been developed based on the autocrine and/or the paracrine capacity of FGF2.
Presta
M
M
Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
Rusnati
M
M
Dell'Era
P
P
Tanghetti
E
E
Urbinati
C
C
Giuliani
R
R
Leali
D
D
D020533:Angiogenesis Inhibitors; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011108:Polymers; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology; D013451:Sulfonic Acids; D014162:Transfection; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D011108:Polymers; D013451:Sulfonic Acids; D016222:Fibroblast Growth Factor 2