Somatostatin receptors in gliomas

Held‐Feindt, Janka; Krisch, Brigitte; Forstreuter, Frauke; Mentlein, Rolf

doi:10.1016/s0928-4257(00)00213-8

Cited by 16 publications

(13 citation statements)

References 39 publications

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“…In glioma cells, stimulation of sst 2 induces multiple signal transduction pathways (Held-Feindt et al 2000). So far, the following pathways have been identified: the inhibition of adenylyl cyclase that lowers elevated cAMP levels, the activation of the protein tyrosine phosphatase SHP-2 that results in the dephosphorylation of activated growth factor receptors, and the hyperpolarisation of inwardly rectifying potassium channels.…”

Section: Discussionmentioning

confidence: 99%

Topology of the signal transduction of the G protein-coupled somatostatin receptor sst 2 in human glioma cells

Mentlein

Held‐Feindt

Krisch

2001

Cell and Tissue Research

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By a dual approach, using electron microscopy and biochemical techniques, we investigated the topology of the somatostatin receptor sst2 with its inhibitory G protein Gialpha after ligand-induced stimulation and internalization in human glioma cells. On intact cells, the sst2 was labeled at 8 degrees C by an antibody directed to its extracellular sequence followed by a 15-nm gold-labeled secondary antibody. In the presence of the ligand, internalization was induced by exposure to 37 degrees C for 5-10 min. Then, cells were either fixed for immunoelectron-microscopic analysis or homogenized for density gradient separation. After post-embedding staining of the sst2-labeled sections with anti-Gialpha1- 3 or anti-caveolin, a co-localization of sst2, Gialpha and caveolin was detected in endosomal vesicles after 5 min of internalization, but not after 10 min. Furthermore, the gold-labeled organelles containing the internalised receptor were separated from the non-labeled ones on sucrose gradients (density shift separation) and analyzed by Western blotting. Also here, in fractions with higher densities, sst2 could be costained with Gialpha and caveolin after 5 min. From these congruent results from both methods, it can be concluded that, in human glioma cells, the receptor sst2 (1) is internalised in caveolin-positive vesicles and (2) is neighboured to its Gialpha proteins at the plasma membrane and early endosomes.

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Section: Discussionmentioning

confidence: 99%

Topology of the signal transduction of the G protein-coupled somatostatin receptor sst 2 in human glioma cells

Mentlein

Held‐Feindt

Krisch

2001

Cell and Tissue Research

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“…Glioblastoma multiforme (GBM), the most aggressive primary brain cancer, expresses multiple SST receptors [214], being sst1 and sst2 the most frequent in both glioma tissues and cell lines [133, 215]. In vitro , the activation of SST receptors leads to antiproliferative and anti-invasive effects [133, 216].…”

Section: Somatostatin and Somatostatin Receptors In Non-endocrine mentioning

confidence: 99%

Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm

Barbieri

Bajetto

Pattarozzi

et al. 2013

International Journal of Peptides

108

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Peptide receptors involved in pathophysiological processes represent promising therapeutic targets. Neuropeptide somatostatin (SST) is produced by specialized cells in a large number of human organs and tissues. SST primarily acts as inhibitor of endocrine and exocrine secretion via the activation of five G-protein-coupled receptors, named sst1–5, while in central nervous system, SST acts as a neurotransmitter/neuromodulator, regulating locomotory and cognitive functions. Critical points of SST/SST receptor biology, such as signaling pathways of individual receptor subtypes, homo- and heterodimerization, trafficking, and cross-talk with growth factor receptors, have been extensively studied, although functions associated with several pathological conditions, including cancer, are still not completely unraveled. Importantly, SST exerts antiproliferative and antiangiogenic effects on cancer cells in vitro, and on experimental tumors in vivo. Moreover, SST agonists are clinically effective as antitumor agents for pituitary adenomas and gastro-pancreatic neuroendocrine tumors. However, SST receptors being expressed by tumor cells of various tumor histotypes, their pharmacological use is potentially extendible to other cancer types, although to date no significant results have been obtained. In this paper the most recent findings on the expression and functional roles of SST and SST receptors in tumor cells are discussed.

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“…Competition binding experiments were performed in membrane homogenates from rat C6 glioma cells/from rat brain cortex, predominantly expressing SSTR2 . In both cases, results of receptor binding studies are almost the same.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, radiolabeling, and preclinical evaluation of a new octreotide analog for somatostatin receptor‐positive tumor scintigraphy

Kyle

Bhowmik

Behera

et al. 2012

Journal of Peptide Science

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Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of >96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.

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Somatostatin receptors in gliomas

Cited by 16 publications

References 39 publications

Topology of the signal transduction of the G protein-coupled somatostatin receptor sst 2 in human glioma cells

Topology of the signal transduction of the G protein-coupled somatostatin receptor sst 2 in human glioma cells

Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm

Synthesis, radiolabeling, and preclinical evaluation of a new octreotide analog for somatostatin receptor‐positive tumor scintigraphy

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