Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor

Cancer Res. 1990 Mar 15;50(6):1774-8.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatography
  • Chromatography, Affinity
  • Chromatography, High Pressure Liquid
  • Durapatite
  • Guinea Pigs
  • Hydroxyapatites
  • Lymphokines / isolation & purification*
  • Lymphokines / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Neoplasms, Experimental / metabolism*
  • Sequence Homology, Nucleic Acid
  • Tumor Cells, Cultured / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Hydroxyapatites
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Durapatite