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. 1996 Apr;188(Pt 2):361–366.

Expression of the vascular endothelial growth factor receptor, KDR, in human placenta.

M Vuckovic 1, J Ponting 1, B I Terman 1, V Niketic 1, M W Seif 1, S Kumar 1
PMCID: PMC1167572  PMID: 8621335

Abstract

Vascular endothelial growth factor (VEGF) is a heparin-binding growth factor known to act directly on vascular endothelial cells by promoting cell proliferation and permeability. To date, 3 structurally related cell surface receptors for VEGF, Flt-1, Flt-4 and KDR, have been identified and shown to be human type III receptor tyrosine kinases. The establishment of a vascular network is crucial to the development of the placenta and occurs through both angiogenesis and vasculogenesis. The signals controlling these processes are unclear. Immunohistochemical and in situ hybridisation techniques have localised VEGF in the trophoblast layers and VEGF binding to placental vascular endothelial cells and haemangioblasts has been shown, suggesting a role for VEGF and its receptors in development of the vascular network. In this study we have used specific antibodies to localise KDR and endothelial cells in 1st and 3rd trimester human placenta. The staining showed a colocalisation of KDR with endothelial cells and haemangioblasts. No staining of trophoblast cells was observed, but strong staining of the endothelial cells was seen in the villous stroma adjacent to areas of trophoblast proliferation.

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Selected References

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

  1. Barleon B., Hauser S., Schöllmann C., Weindel K., Marmé D., Yayon A., Weich H. A. Differential expression of the two VEGF receptors flt and KDR in placenta and vascular endothelial cells. J Cell Biochem. 1994 Jan;54(1):56–66. doi: 10.1002/jcb.240540107. [DOI] [PubMed] [Google Scholar]
  2. Charnock-Jones D. S., Sharkey A. M., Boocock C. A., Ahmed A., Plevin R., Ferrara N., Smith S. K. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells. Biol Reprod. 1994 Sep;51(3):524–530. doi: 10.1095/biolreprod51.3.524. [DOI] [PubMed] [Google Scholar]
  3. Demir R., Kaufmann P., Castellucci M., Erbengi T., Kotowski A. Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat (Basel) 1989;136(3):190–203. doi: 10.1159/000146886. [DOI] [PubMed] [Google Scholar]
  4. Dougher-Vermazen M., Hulmes J. D., Böhlen P., Terman B. I. Biological activity and phosphorylation sites of the bacterially expressed cytosolic domain of the KDR VEGF-receptor. Biochem Biophys Res Commun. 1994 Nov 30;205(1):728–738. doi: 10.1006/bbrc.1994.2726. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Eaton B. M., Leach L., Firth J. A. Permeability of the fetal villous microvasculature in the isolated perfused term human placenta. J Physiol. 1993 Apr;463:141–155. doi: 10.1113/jphysiol.1993.sp019588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Ferriani R. A., Charnock-Jones D. S., Prentice A., Thomas E. J., Smith S. K. Immunohistochemical localization of acidic and basic fibroblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction. Hum Reprod. 1993 Jan;8(1):11–16. doi: 10.1093/oxfordjournals.humrep.a137856. [DOI] [PubMed] [Google Scholar]
  9. Gonzalez A. M., Buscaglia M., Ong M., Baird A. Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues. J Cell Biol. 1990 Mar;110(3):753–765. doi: 10.1083/jcb.110.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham C. H., Lala P. K. Mechanisms of placental invasion of the uterus and their control. Biochem Cell Biol. 1992 Oct-Nov;70(10-11):867–874. doi: 10.1139/o92-135. [DOI] [PubMed] [Google Scholar]
  11. Jackson M. R., Carney E. W., Lye S. J., Ritchie J. W. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta. 1994 Jun;15(4):341–353. doi: 10.1016/0143-4004(94)90002-7. [DOI] [PubMed] [Google Scholar]
  12. Jakeman L. B., Armanini M., Phillips H. S., Ferrara N. Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology. 1993 Aug;133(2):848–859. doi: 10.1210/endo.133.2.7688292. [DOI] [PubMed] [Google Scholar]
  13. Jones C. J., Fox H. Ultrastructure of the normal human placenta. Electron Microsc Rev. 1991;4(1):129–178. doi: 10.1016/0892-0354(91)90019-9. [DOI] [PubMed] [Google Scholar]
  14. Klagsbrun M., Soker S. VEGF/VPF: the angiogenesis factor found? Curr Biol. 1993 Oct 1;3(10):699–702. doi: 10.1016/0960-9822(93)90073-w. [DOI] [PubMed] [Google Scholar]
  15. Klagsbrun M. The fibroblast growth factor family: structural and biological properties. Prog Growth Factor Res. 1989;1(4):207–235. doi: 10.1016/0955-2235(89)90012-4. [DOI] [PubMed] [Google Scholar]
  16. Koch A. E., Harlow L. A., Haines G. K., Amento E. P., Unemori E. N., Wong W. L., Pope R. M., Ferrara N. Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol. 1994 Apr 15;152(8):4149–4156. [PubMed] [Google Scholar]
  17. Maglione D., Guerriero V., Viglietto G., Delli-Bovi P., Persico M. G. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9267–9271. doi: 10.1073/pnas.88.20.9267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Midy V., Plouët J. Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem Biophys Res Commun. 1994 Feb 28;199(1):380–386. doi: 10.1006/bbrc.1994.1240. [DOI] [PubMed] [Google Scholar]
  19. Millauer B., Wizigmann-Voos S., Schnürch H., Martinez R., Møller N. P., Risau W., Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 1993 Mar 26;72(6):835–846. doi: 10.1016/0092-8674(93)90573-9. [DOI] [PubMed] [Google Scholar]
  20. Pepper M. S., Ferrara N., Orci L., Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun. 1992 Dec 15;189(2):824–831. doi: 10.1016/0006-291x(92)92277-5. [DOI] [PubMed] [Google Scholar]
  21. Presta M. Sex hormones modulate the synthesis of basic fibroblast growth factor in human endometrial adenocarcinoma cells: implications for the neovascularization of normal and neoplastic endometrium. J Cell Physiol. 1988 Dec;137(3):593–597. doi: 10.1002/jcp.1041370329. [DOI] [PubMed] [Google Scholar]
  22. Quinn T. P., Peters K. G., De Vries C., Ferrara N., Williams L. T. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7533–7537. doi: 10.1073/pnas.90.16.7533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ravindranath N., Little-Ihrig L., Phillips H. S., Ferrara N., Zeleznik A. J. Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary. Endocrinology. 1992 Jul;131(1):254–260. doi: 10.1210/endo.131.1.1612003. [DOI] [PubMed] [Google Scholar]
  24. Sharkey A. M., Charnock-Jones D. S., Boocock C. A., Brown K. D., Smith S. K. Expression of mRNA for vascular endothelial growth factor in human placenta. J Reprod Fertil. 1993 Nov;99(2):609–615. doi: 10.1530/jrf.0.0990609. [DOI] [PubMed] [Google Scholar]
  25. Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990 Apr;5(4):519–524. [PubMed] [Google Scholar]
  26. Shweiki D., Itin A., Neufeld G., Gitay-Goren H., Keshet E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest. 1993 May;91(5):2235–2243. doi: 10.1172/JCI116450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Terman B. I., Dougher-Vermazen M., Carrion M. E., Dimitrov D., Armellino D. C., Gospodarowicz D., Böhlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1579–1586. doi: 10.1016/0006-291x(92)90483-2. [DOI] [PubMed] [Google Scholar]
  28. Wang J. M., Kumar S., Pye D., van Agthoven A. J., Krupinski J., Hunter R. D. A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. Int J Cancer. 1993 May 28;54(3):363–370. doi: 10.1002/ijc.2910540303. [DOI] [PubMed] [Google Scholar]
  29. de Vries C., Escobedo J. A., Ueno H., Houck K., Ferrara N., Williams L. T. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989–991. doi: 10.1126/science.1312256. [DOI] [PubMed] [Google Scholar]

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