title: Expression and function of somatostatin receptors in peripheral nerve sheath tumors.
abstract: Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations. In contrast, sst2A mRNA and protein was present in 89% of schwannomas. This receptor subtype was less frequently detected in neurofibromas (22%) and MPNSTs (15%). Interestingly, sst4 was seen in 32% of MPNSTs and was almost exclusively expressed in this malignant tumor type. In support of a role in Schwann cell tumor growth control by somatostatin was the observation of induced internalization of sst2A and inhibition of cell proliferation in an NF1-associated MPNST cell line. Moreover, administration of an sst2A-selective agonist resulted in induction of MPNST cell apoptosis. We conclude that peripheral nerve sheath tumors often express at least one functional somatostatin receptor. Furthermore, our findings suggest a potential clinical role for somatostatin receptor agonists in tumor imaging and/or treatment of schwannomas and MPNSTs.
authors.affiliation: Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany. christian.mawrin@medizin.uni-magdeburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Anja
authors.initials: A
authors.lastname: Hellwig-Patyk
authors.forename: Elmar
authors.initials: E
authors.lastname: Kirches
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.forename: Raimund
authors.initials: R
authors.lastname: Firsching
authors.forename: Christian K
authors.initials: CK
authors.lastname: Vorwerk
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Knut
authors.initials: K
authors.lastname: Dietzmann
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grimm
authors.forename: Guy
authors.initials: G
authors.lastname: Lindberg
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018317:Nerve Sheath Neoplasms / Q000378:metabolism* / Q000473:pathology; D009442:Neurilemmoma / Q000378:metabolism*; D009456:Neurofibromatosis 1 / Q000378:metabolism* / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D017481:Receptors, Somatostatin