Skip to main content
Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1992 Feb;3(2):211–220. doi: 10.1091/mbc.3.2.211

Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.

B Berse 1, L F Brown 1, L Van de Water 1, H F Dvorak 1, D R Senger 1
PMCID: PMC275520  PMID: 1550962

Abstract

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), increases microvascular permeability and is a specific mitogen for endothelial cells. Expression of VPF/VEGF previously was demonstrated in a variety of tumor cells, in cultures of pituitary-derived cells, and in corpus luteum. Here we present evidence, by Northern analysis and in situ hybridization, that the VPF/VEGF gene is expressed in many adult organs, including lung, kidney, adrenal gland, heart, liver, and stomach mucosa, as well as in elicited peritoneal macrophages. The highest levels of VPF/VEGF transcripts were found in epithelial cells of lung alveoli, renal glomeruli and adrenal cortex, and in cardiac myocytes. The prominence of VPF/VEGF mRNA in these tissues suggests a possible role for VPF/VEGF in regulating baseline microvascular permeability, which is essential for tissue nutrition and waste removal. We also demonstrate particularly high VPF/VEGF mRNA levels in several human tumors, where it may be involved in promoting tumor angiogenesis and stroma generation, both as an endothelial cell mitogen and indirectly by its permeability enhancing effect that leads to the deposition of a provisional fibrin gel matrix.

Full text

PDF
212

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams D. O., Hamilton T. A. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2:283–318. doi: 10.1146/annurev.iy.02.040184.001435. [DOI] [PubMed] [Google Scholar]
  2. Betsholtz C., Rorsman F., Westermark B., Ostman A., Heldin C. H. Analogous alternative splicing. Nature. 1990 Mar 22;344(6264):299–299. doi: 10.1038/344299a0. [DOI] [PubMed] [Google Scholar]
  3. Brock T. A., Dvorak H. F., Senger D. R. Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol. 1991 Jan;138(1):213–221. [PMC free article] [PubMed] [Google Scholar]
  4. Clauss M., Gerlach M., Gerlach H., Brett J., Wang F., Familletti P. C., Pan Y. C., Olander J. V., Connolly D. T., Stern D. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med. 1990 Dec 1;172(6):1535–1545. doi: 10.1084/jem.172.6.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conn G., Bayne M. L., Soderman D. D., Kwok P. W., Sullivan K. A., Palisi T. M., Hope D. A., Thomas K. A. Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2628–2632. doi: 10.1073/pnas.87.7.2628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conn G., Soderman D. D., Schaeffer M. T., Wile M., Hatcher V. B., Thomas K. A. Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1323–1327. doi: 10.1073/pnas.87.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connolly D. T., Olander J. V., Heuvelman D., Nelson R., Monsell R., Siegel N., Haymore B. L., Leimgruber R., Feder J. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem. 1989 Nov 25;264(33):20017–20024. [PubMed] [Google Scholar]
  8. Dvorak H. F., Galli S. J., Dvorak A. M. Cellular and vascular manifestations of cell-mediated immunity. Hum Pathol. 1986 Feb;17(2):122–137. doi: 10.1016/s0046-8177(86)80285-4. [DOI] [PubMed] [Google Scholar]
  9. Dvorak H. F., Orenstein N. S., Carvalho A. C., Churchill W. H., Dvorak A. M., Galli S. J., Feder J., Bitzer A. M., Rypysc J., Giovinco P. Induction of a fibrin-gel investment: an early event in line 10 hepatocarcinoma growth mediated by tumor-secreted products. J Immunol. 1979 Jan;122(1):166–174. [PubMed] [Google Scholar]
  10. Dvorak H. F., Sioussat T. M., Brown L. F., Berse B., Nagy J. A., Sotrel A., Manseau E. J., Van de Water L., Senger D. R. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med. 1991 Nov 1;174(5):1275–1278. doi: 10.1084/jem.174.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. Ferrara N., Henzel W. J. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):851–858. doi: 10.1016/0006-291x(89)92678-8. [DOI] [PubMed] [Google Scholar]
  13. Ffrench-Constant C., Van de Water L., Dvorak H. F., Hynes R. O. Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat. J Cell Biol. 1989 Aug;109(2):903–914. doi: 10.1083/jcb.109.2.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gospodarowicz D., Abraham J. A., Schilling J. Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7311–7315. doi: 10.1073/pnas.86.19.7311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hammond M. E., Dvorak H. F. Antigen-induced stimulation of glucosamine incorporation by guinea pig peritoneal macrophages in delayed hypersensitivity. J Exp Med. 1972 Dec 1;136(6):1518–1532. doi: 10.1084/jem.136.6.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Keck P. J., Hauser S. D., Krivi G., Sanzo K., Warren T., Feder J., Connolly D. T. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309–1312. doi: 10.1126/science.2479987. [DOI] [PubMed] [Google Scholar]
  17. Leung D. W., Cachianes G., Kuang W. J., Goeddel D. V., Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989 Dec 8;246(4935):1306–1309. doi: 10.1126/science.2479986. [DOI] [PubMed] [Google Scholar]
  18. Meinkoth J., Wahl G. Hybridization of nucleic acids immobilized on solid supports. Anal Biochem. 1984 May 1;138(2):267–284. doi: 10.1016/0003-2697(84)90808-x. [DOI] [PubMed] [Google Scholar]
  19. Nagy J. A., Brown L. F., Senger D. R., Lanir N., Van de Water L., Dvorak A. M., Dvorak H. F. Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta. 1989 Feb;948(3):305–326. doi: 10.1016/0304-419x(89)90004-8. [DOI] [PubMed] [Google Scholar]
  20. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Phillips H. S., Hains J., Leung D. W., Ferrara N. Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology. 1990 Aug;127(2):965–967. doi: 10.1210/endo-127-2-965. [DOI] [PubMed] [Google Scholar]
  22. Plouët J., Schilling J., Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J. 1989 Dec 1;8(12):3801–3806. doi: 10.1002/j.1460-2075.1989.tb08557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Senger D. R., Connolly D. T., Van de Water L., Feder J., Dvorak H. F. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990 Mar 15;50(6):1774–1778. [PubMed] [Google Scholar]
  24. Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985. doi: 10.1126/science.6823562. [DOI] [PubMed] [Google Scholar]
  25. Senger D. R., Perruzzi C. A., Feder J., Dvorak H. F. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986 Nov;46(11):5629–5632. [PubMed] [Google Scholar]
  26. Tischer E., Gospodarowicz D., Mitchell R., Silva M., Schilling J., Lau K., Crisp T., Fiddes J. C., Abraham J. A. Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1198–1206. doi: 10.1016/0006-291x(89)92729-0. [DOI] [PubMed] [Google Scholar]
  27. Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., Fiddes J. C., Abraham J. A. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947–11954. [PubMed] [Google Scholar]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology

RESOURCES