Neurotensin high affinity binding sites and endopeptidase 24.11 are present respectively in the meningothelial and in the fibroblastic components of human meningiomas

Abstract The presence of neurotensin receptors and endopeptidase 24.11 (E-24.11) in 16 human meningioma specimens, obtained at surgery, was assessed by measuring the binding of 125 I-[tyrosyl 3 ]neurotensin(1–13) ( 125 I-NT) and the inhibitor 3 H-N((2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine ( 3 H-HACBO-Gly), for the receptor and enzyme, respectively. E-24.11 activity was also measured. Autoradiography, on the 16 meningiomas, showed that specific 125 I-NT labeling (nonspecific labeling was assessed in the presence of excess NT) was exclusively located in the meningothelial regions. In contrast, specific 3 H-HACBO-Gly labeling (nonspecific labeling was assessed in the presence of an excess of the E-24.11 inhibitor thiorphan) was exclusively found in fibroblastic regions. No specific labeling of either ligand was found on collagen or blood vessels. In vitro binding assays were performed on membranes of 10 of the 16 meningiomas. In the 4 meningiomas rich in meningothelial cells, 125 I-NT specifically bound to one population of sites with B max ranging from 57 to 405 fmol/mg protein and K d around 0.3 nM. These sites share common properties with the brain NT receptor, since the carboxy terminal acetyl NT(8–13) fragment bound to the same sites but with a higher affinity. The carboxy terminal analogue of NT, neuromedin N, also bound to the same sites with a 10-fold lower affinity and the sites were bradykinin and levocabastine insensitive. In the 4 meningiomas rich in fibroblastic cells, 3 H-HACBO-Gly specifically bound to one population of sites with B max ranging from 251 to 739 fmol/mg protein and K d around 2.8 nM. In agreement with the binding data, E-24.11 activity, expressed in fmol 3 H-[D-Ala 2 ]leucine enkephalin degraded/min/mg protein, ranged from 102 to 281 and was specifically inhibited by the E-24.11 inhibitor retrothiorphan R, indicating the presence of biologically active E-24.11 in the meningiomas. In the 2 meningiomas poor in tumoral cells and rich in collagen bundles, no specific binding was found with either ligand. The presence, in abundance, of NT receptors and E-24.11 on the meningothelial components and on the fibroblastic components of the meningiomas, respectively, is a new indicator of the duality of the arachnoid cell from which these tumors arise. These markers may be useful for the classification of the histologic phenotypes of the meningiomas, and for clinical diagnosis of small meningiomas using SPECT and for the treatment of surgically inaccessible meningiomas.