Home LiteratureArticle Details
PMID: 7856749 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors.

The American journal of pathology ·Vol. 146 ·No. 2 ·1995-02-00 ·Pages 368-78

Hatva E, Kaipainen A, Mentula P, Jääskeläinen J, Paetau A, Haltia M, Alitalo K

Abstract

Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis.

MeSH Terms
Adult Aged Brain Neoplasms/chemistry,enzymology,secondary Child Endothelial Growth Factors/analysis Female Glioma/chemistry,enzymology Humans Immunohistochemistry In Situ Hybridization Lymphokines/analysis Male Melanoma/chemistry,enzymology,secondary Meningioma/chemistry,enzymology Middle Aged Placenta Growth Factor Pregnancy Proteins/analysis RNA, Messenger/analysis Receptor Protein-Tyrosine Kinases/analysis Receptors, Growth Factor/analysis Receptors, Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Lymphokines PGF protein, human Pregnancy Proteins RNA, Messenger Receptors, Growth Factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Placenta Growth Factor Receptor Protein-Tyrosine Kinases Receptors, Vascular Endothelial Growth Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hatva E
Department of Pathology, University of Helsinki, Finland.
Kaipainen A
Mentula P
Jääskeläinen J
Paetau A
Haltia M
Alitalo K
References (37)
37 references, click to expand
  1. Angiogenesis.
    J Biol Chem. 1992 Jun 5;267(16):10931-4 PMID: 1375931
  2. The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells.
    J Exp Med. 1993 Dec 1;178(6):2077-88 PMID: 8245783
  3. tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors.
    Oncogene. 1992 Aug;7(8):1471-80 PMID: 1630810
  4. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines.
    Cancer Res. 1992 Oct 15;52(20):5738-43 PMID: 1327515
  5. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor.
    Biochem Biophys Res Commun. 1992 Sep 30;187(3):1579-86 PMID: 1417831
  6. Enhanced expression of the tie receptor tyrosine kinase in endothelial cells during neovascularization.
    Blood. 1992 Nov 15;80(10):2548-55 PMID: 1384789
  7. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer.
    Lancet. 1992 Nov 7;340(8828):1120-4 PMID: 1279332
  8. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.
    Nature. 1992 Oct 29;359(6398):843-5 PMID: 1279431
  9. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo.
    Nature. 1992 Oct 29;359(6398):845-8 PMID: 1279432
  10. Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms.
    J Clin Invest. 1993 Jan;91(1):153-9 PMID: 8380810
  11. Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells.
    Oncogene. 1993 Feb;8(2):395-405 PMID: 8426746
  12. Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta.
    Oncogene. 1993 Mar;8(3):663-70 PMID: 8382358
  13. Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.
    Oncogene. 1993 Apr;8(4):925-31 PMID: 7681160
  14. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis.
    Cell. 1993 Mar 26;72(6):835-46 PMID: 7681362
  15. Synthesis of von Willebrand factor by cultured human endothelial cells.
    Proc Natl Acad Sci U S A. 1974 May;71(5):1906-9 PMID: 4209883
  16. Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors.
    Proc Natl Acad Sci U S A. 1980 Sep;77(9):5258-62 PMID: 6254071
  17. Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo.
    Cell. 1987 Jul 3;50(1):79-88 PMID: 3594565
  18. A molecular analysis of mouse development from 8 to 10 days post coitum detects changes only in embryonic globin expression.
    Development. 1987 Apr;99(4):493-500 PMID: 2444404
  19. Fibroblast growth factors.
    FASEB J. 1987 Dec;1(6):434-40 PMID: 3315806
  20. The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0 mm thick) skin melanoma. A quantitative histologic study.
    Am J Pathol. 1988 Nov;133(2):419-23 PMID: 3189515
  21. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.
    Biochem Biophys Res Commun. 1989 Jun 15;161(2):851-8 PMID: 2735925
  22. 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):7311-5 PMID: 2798412
  23. Vascular permeability factor, an endothelial cell mitogen related to PDGF.
    Science. 1989 Dec 8;246(4935):1309-12 PMID: 2479987
  24. What is the evidence that tumors are angiogenesis dependent?
    J Natl Cancer Inst. 1990 Jan 3;82(1):4-6 PMID: 1688381
  25. 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):1323-7 PMID: 2406719
  26. 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):519-24 PMID: 2158038
  27. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
    N Engl J Med. 1991 Jan 3;324(1):1-8 PMID: 1701519
  28. Identification of a new endothelial cell growth factor receptor tyrosine kinase.
    Oncogene. 1991 Sep;6(9):1677-83 PMID: 1656371
  29. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9026-30 PMID: 1717995
  30. 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):9267-71 PMID: 1924389
  31. FLT4, a novel class III receptor tyrosine kinase in chromosome 5q33-qter.
    Cancer Res. 1992 Feb 1;52(3):746-8 PMID: 1310071
  32. The vascular endothelial growth factor family of polypeptides.
    J Cell Biochem. 1991 Nov;47(3):211-8 PMID: 1791185
  33. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.
    Science. 1992 Feb 21;255(5047):989-91 PMID: 1312256
  34. A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.
    Mol Cell Biol. 1992 Apr;12(4):1698-707 PMID: 1312667
  35. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.
    Nature. 1993 Apr 29;362(6423):841-4 PMID: 7683111
  36. The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor.
    Oncogene. 1993 May;8(5):1233-40 PMID: 8386825
  37. Relation of neovascularisation to metastasis of non-small-cell lung cancer.
    Lancet. 1992 Jul 18;340(8812):145-6 PMID: 1378165
Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1995-02-00
Pages
368-78
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1869858
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2