Expression of somatostatin receptor subtypes in human brain tumors

Abstract

Expression of mRNA for the 5 somatostatin receptors (sst1-5) was characterized by Northern blot and RT-PCR analysis in 20 meningioma and 9 glioma samples. sst1 mRNA was detectable by Northern blots of poly-A+ RNA in meningiomas but not gliomas. In contrast, sst2 mRNA was readily detected by Northern blots of total RNA as a major 2.3 kb transcript and 2 minor 4.3 kb and 8 kb transcripts in all meningiomas and 6 out of 9 gliomas. Quantitation of the 2.3 kb sst2 mRNA showed that 15 out of 20 tumors expressed 1.3- to 33-fold higher levels than control normal human brain. Mean sst2 mRNA for the 20 meningioma samples was 978% that of normal brain. Three gliomas showed 7- to 14-fold higher sst2 mRNA than normal brain whereas the remaining samples displayed very low or undetectable levels. Immunocytochemistry of meningioma and glioma samples, with a sst2-specific antibody revealed immunoreactivity in tumor cells and peritumoral tissue, with prominent expression in blood vessels. mRNA for sst3,4,5 could not be detected by Northern blots in any of the tumors. RT-PCR analysis of meningiomas and gliomas revealed the following percent of tumors positive for a given sst mRNA: sst1 (86%), sst2 (100%), sst3 (60%), sst4 (58%), and sst5 (67%); 85% of tumors expressed 3 of the 5 subtypes. No correlation was found between the pattern of expression of sst mRNA and tumor type, location, and histology for either the meningiomas or gliomas. Our results show that meningiomas and gliomas are all positive for at least one sst subtype, the majority expressing multiple subtypes. sst2 is the most abundant isoform with a rich expression in both tumor and peritumoral tissue especially blood vessels.