Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.

TLDR

Vascular permeability factor (VPF) is a 40‑kDa protein purified from guinea pig tumor cells that increases blood vessel fluid permeability when injected intradermally. The authors confirmed VPF’s identity and activity by matching its 40‑kDa size, isoform pattern, unique N‑terminal sequence, and immunoadsorption profile, and showed it binds with high affinity to a specific endothelial cell surface receptor. VPF uniquely stimulates endothelial cell proliferation and angiogenesis in vitro and in vivo, without affecting other cell types, and its high‑affinity binding to endothelial receptors underlies this selective activity.

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 (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 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 permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis.