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 cardiovascul ar system, ET-1 has been shown to constitute a potent growth regulator y peptide in various tissues. We have studied the expression of ET-1 a nd its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as we ll as their involvement in cellular growth. By PCR of reverse-transcri bed 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 examine d. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumo ral cells was observed by in situ hybridization and immunohistochemist ry, whereas ET-Br mRNA was expressed at low level only in cells belong ing to blood vessels, In addition, we found that ET-1 stimulated [H-3] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist fo r 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 evi dence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert wit h other growth factors and cytokines, is involved in the meningioma tu morigenesis.