Purification and NH2-Terminal Amino Acid Sequence of Guinea Pig Tumor-secreted Vascular Permeability Factor

DR Senger, DT Connolly, L Van De Water, J Feder… - Cancer research, 1990 - AACR
DR Senger, DT Connolly, L Van De Water, J Feder, HF Dvorak
Cancer research, 1990AACR
Rodent and human tumor cell lines secrete a potent vascular permeability factor (VPF)
which causes a rapid and substantial increase in microvascular permeability to plasma
proteins without causing mast cell degranulation, or endothelial cell damage or without
exciting an inflammatory cell infiltrate [DR Senger, SJ Galli, AM Dvorak, CA Perruzzi, VS
Harvey, and HF Dvorak. Science (Wash. DC), 219: 983–985, 1983; DR Senger, CA Perruzzi,
J. Feder, and HF Dvorak. Cancer Res., 46: 5629–5632, 1986]. VPF now has been purified to …
Abstract
Rodent and human tumor cell lines secrete a potent vascular permeability factor (VPF) which causes a rapid and substantial increase in microvascular permeability to plasma proteins without causing mast cell degranulation, or endothelial cell damage or without exciting an inflammatory cell infiltrate [D. R. Senger, S. J. Galli, A. M. Dvorak, C. A. Perruzzi, V. S. Harvey, and H. F. Dvorak. Science (Wash. DC), 219: 983–985, 1983; D. R. Senger, C. A. Perruzzi, J. Feder, and H. F. Dvorak. Cancer Res., 46: 5629–5632, 1986]. VPF now has been purified to homogeneity from guinea pig tumor cell culture medium; it is a Mr 34,000–43,000 protein, and a NH2-terminal amino acid sequence has been derived. A synthetic peptide corresponding to amino acid residues 1–24 of the native protein was used to raise rabbit antibodies which bind all of the vessel permeability-increasing activity secreted by guinea pig tumor cells and which stain purified VPF on immunoblots. These findings establish that this NH2-terminal amino acid sequence was derived from the permeability factor. Homology searches found no identity or close similarity between VPF NH2-terminal sequence and database sequences, indicating that VPF is distinct from other proteins for which sequence data are available. In particular, no sequence similarity was found between tumor-secreted VPF and other mediators of increased vessel permeability including plasma and glandular kallikreins.
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