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Somatostatin and somatostatin receptors in the diagnosis and treatment of gliomas

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Abstract

Somatostatin analogues are in clinical use for thediagnosis and treatment of several oncological indications, namelypituitary adenomas and endocrine gastrointestinal tumors. In additionfor a variety of malignancies their potential valueis being studied. It has been speculated thatsomatostatin plays a role in the homeostasis ofgliomas, and that gliomas could be susceptible toantiproliferative effects of somatostatin analogues. These assumptions weretested in 20 human cell lines derived frommalignant gliomas and 4 glioblastoma tissue specimens, whichwere analyzed for their expression of the fiveknown somatostatin receptor genes (SSTR1–5) and for thereceptor function. Using semiquantitative PCR techniques, SSTR2 transcriptswere found in all 20 cell lines and4 glioblastomas, SSTR1 transcripts were detected in 9cell lines and 4 glioblastomas, and SSTR3 transcriptswere noted in 7 cell lines and 1glioblastoma. SSTR4 and SSTR5 transcripts were only rarelydetected. Gene expression profiles in glioblastoma tissue specimensresembled those of the cell lines in qualityas well as quantity, with average transcript levelsbeing highest for the SSTR2, followed by SSTR1and SSTR3. However, when compared to GH 3 anteriorpituitary tumor cells, the relative amounts of PCRamplified DNA fragments were found to be atleast 120 fold lower in glioblastoma cell linesand tumor specimens. Binding studies indicated that glioblastomaderived cells contained only minute amounts of SSTRs.No inhibition of proliferation was observed when 10selected cell lines were incubated with somatostatin-14 (SST-14)or octreotide (SMS 201 -995) at concentrations ranging from10-9 -6M, however, the proliferationof two cell lines was weakly stimulated after6 days of incubation with 10-6 octreotide.The activity of adenylate cyclase, stimulated by forskolin,was inhibited by maximally 25% at 10-6 MSST-14 or octreotide in one of 5 selectedglioblastoma cell lines. Somatostatin peptides do not seemto exert anti-proliferative effects on glioblastoma cells andtherefore appear to be of no obvious valuefor glioblastoma therapy. Most likely the amount ofcell surface SSTRs is not sufficient to mediateantiproliferative effects. Since it has been described thatSSTRs are detectable on most differentiated gliomas aswell as astrocytes, it may be speculated thatSSTRs may be relevant only in the contextof well differentiated cellular programs but lose theirsignificance with progressive dedifferentiation.

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Authors and Affiliations

  1. Laboratory for Brain Tumor Biology, Department of Neurological Surgery, University Hospital Eppendorf, Hamburg, Germany

    Katrin Lamszus & Manfred Westphal

  2. Department of Molecular Genetics, German Institute of Human Nutrition, and University of Potsdam, Potsdam, Germany

    Wolfgang Meyerhof

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  1. Katrin Lamszus
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Lamszus, K., Meyerhof, W. & Westphal, M. Somatostatin and somatostatin receptors in the diagnosis and treatment of gliomas. J Neurooncol 35, 353–364 (1997). https://doi.org/10.1023/A:1005893223090

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