Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth.
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.
Pagotto
U
U
Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Arzberger
T
T
Hopfner
U
U
Sauer
J
J
Renner
U
U
Newton
C J
CJ
Lange
M
M
Uhl
E
E
Weindl
A
A
Stalla
G K
GK
D000328:Adult; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis; D016232:Endothelins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D008578:Meninges / Q000737:chemistry; D008579:Meningioma / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017466:Receptors, Endothelin / Q000032:analysis* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016232:Endothelins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D004247:DNA