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PMID: 7560095 Published · ppublish English Journal Article

Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth.

The Journal of clinical investigation ·Vol. 96 ·No. 4 ·1995-10-00 ·Pages 2017-25

Pagotto U, Arzberger T, Hopfner U, Sauer J, Renner U, Newton CJ, Lange M, Uhl E, Weindl A, Stalla GK

Abstract

In addition to its well-known homoeostatic actions in the cardiovascular system, ET-1 has been shown to constitute a potent growth regulatory peptide in various tissues. We have studied the expression of ET-1 and its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as well as their involvement in cellular growth. By PCR of reverse-transcribed RNA we detected ET-1 mRNA in 91% (32 of 35), ET-Ar mRNA in 82% (29 of 35), and ET-Br mRNA in 42% (15 of 35) of human meningiomas examined. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumoral cells was observed by in situ hybridization and immunohistochemistry, whereas ET-Br mRNA was expressed at low level only in cells belonging to blood vessels. In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar. In contrast, RES-701-3, an antagonist of ET-Br, did not block the proliferative effect of ET-1. In conclusion, our data provide evidence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert with other growth factors and cytokines, is involved in the meningioma tumorigenesis.

MeSH Terms
Adult Aged Base Sequence DNA/biosynthesis Endothelins/analysis,genetics,physiology Female Humans Male Meningeal Neoplasms/chemistry,pathology Meninges/chemistry Meningioma/chemistry,pathology Middle Aged Molecular Sequence Data Polymerase Chain Reaction RNA, Messenger/analysis Receptors, Endothelin/analysis,physiology Tumor Cells, Cultured
Chemicals
Endothelins RNA, Messenger Receptors, Endothelin DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Pagotto U
Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Arzberger T
Hopfner U
Sauer J
Renner U
Newton C J
Lange M
Uhl E
Weindl A
Stalla G K
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118249
Published
1995-10-00
Pages
2017-25
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC185840
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI118249 PMC Full Text View journal details
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