Expression and function of somatostatin receptors in peripheral nerve sheath tumors

Christian Mawrin, Stefan Schulz, Anja Hellwig-Patyk, Elmar Kirches, Albert Roessner, Uwe Lendeckel, Raimund Firsching, Christian K. Vorwerk, Gerburg Keilhoff, Knut Dietzmann, Kirsten Grimm, Guy Lindberg, David H. Gutmann, Bernd W. Scheithauer, Arie Perry

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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 sst 2A-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.

Original languageEnglish
Pages (from-to)1080-1088
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume64
Issue number12
DOIs
StatePublished - Dec 1 2005

Keywords

  • Malignant peripheral nerve sheath tumor (MPNST)
  • NF1
  • Neurofibroma
  • Peripheral nerve
  • Schwannoma
  • Somatostatin receptor

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    Mawrin, C., Schulz, S., Hellwig-Patyk, A., Kirches, E., Roessner, A., Lendeckel, U., Firsching, R., Vorwerk, C. K., Keilhoff, G., Dietzmann, K., Grimm, K., Lindberg, G., Gutmann, D. H., Scheithauer, B. W., & Perry, A. (2005). Expression and function of somatostatin receptors in peripheral nerve sheath tumors. Journal of neuropathology and experimental neurology, 64(12), 1080-1088. https://doi.org/10.1097/01.jnen.0000190065.36182.25