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• W4361815140 abstract "<div>AbstractPurpose:<p>Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST₂ and SST₅. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST₂. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST₃ and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST₃-agonists and characterize their effects on experimental NFPT models.</p>Experimental Design:<p>Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST₃-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST₃-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST₃-agonist.</p>Results:<p>We successfully identified the first SST₃-agonist peptides. SST₃-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis <i>in vitro</i>, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST₃-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST₃ than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST₃-agonist treatments. Concurrently, <i>SSTR3</i> silencing increased cell viability in a subset of NFPTs.</p>Conclusions:<p>This study demonstrates that SST₃-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST₃, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.</p></div>" @default.
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• W4361815140 date "2023-03-31" @default.
• W4361815140 modified "2023-09-27" @default.
• W4361815140 title "Data from A Somatostatin Receptor Subtype-3 (SST₃) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors" @default.
• W4361815140 doi "https://doi.org/10.1158/1078-0432.c.6530364" @default.
• W4361815140 hasPublicationYear "2023" @default.
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