Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.

Abstract

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (M, 40 kD); (b) multiple isoforms (pI 2 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeabilityenhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore,

Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

“…These functions are essential steps for neovessel sprouting (Kubota et al, 1988;Connolly et al, 1989) and angiogenesis, which is an important biological process involved in metastasis formation (Liotta et al, 1991;Weidner et al, 1991). Importantly, throughout the experiment with the CAM model, this study showed NAMI-A to prevent in vivo angiogenesis at doses known to have anti-metastasis activity.…”

Using guinea pigs in studies relevant to asthma and COPD

“…Many fundamental processes, mediators and regulators of airways disease pathogenesis were discovered or demonstrated first in guinea pigs, including the Schultz-Dale (immediate type hypersensitivity) reaction, the actions of histamine, the cysteinyl-leukotrienes and their two receptors, beta adrenoceptor subtypes, thromboxane, vascular endothelial growth factor (VEGF), eotaxin, alveolar macrophage derived neutrophil chemotactic factor(s) (leukotriene B 4 and/or IL-8) and the roles of cAMP and inositol triphosphate in signal transduction [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Receptor pharmacology in guinea pigs more closely matches that of human receptor pharmacology than most other commonly used species [1,20,21] (Table 1, Figs.…”

The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-γ pathway and partially induces mitotic signals in NIH3T3 fibroblasts

“…Recent studies have revealed that Vascular Endothelial Growth Factor (VEGF), also referred to as Vascular Permeability Factor (VPF), is an important element for many angiogenic processes under normal and abnormal states Shibuya, 1995;Mustonen and Alitro, 1995). VEGF carries two major biological activities, one is the capacity to stimulate vascular endothelial cell proliferation (Ferrara and Henzel, 1989;Leung et al, 1989;Connolly et al, 1989) and the other is the ability to increase microvessel permeability to macromolecules (Senger et al, 1983;Keck et al, 1989). In addition, some additional biological activities have recently been reported: VEGF was found to stimulate macrophage migration (Clauss et al, 1993;Barleon et al, 1996), protease production in endothelial cells (Pepper et al, 1991;Unemori et al, 1992) and the resistance of hematopoietic cells to radiation-induced apoptosis (Katoh et al, 1995).…”