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Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting

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Item Type:Article
Title:Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting
Creators Name:Bolduan, F. and Wetzel, A. and Giesecke, Y. and Eichhorn, I. and Alenina, N. and Bader, M. and Willnow, T.E. and Wiedenmann, B. and Sigal, M.
Abstract:A subset of neuroendocrine tumors (NETs) can cause an excessive secretion of hormones, neuropeptides, and biogenic amines into the bloodstream. These so-called functional NETs evoke a hormone-related disease and lead to several different syndromes, depending on the factors released. One of the most common functional syndromes, carcinoid syndrome, is characterized mainly by over-secretion of serotonin. However, what distinguishes functional from non-functional tumors on a molecular level remains unknown. Here, we demonstrate that the expression of sortilin, a widely expressed transmembrane receptor involved in intracellular protein sorting, is significantly increased in functional compared to non-functional NETs and thus can be used as a biomarker for functional NETs. Furthermore, using a cell line model of functional NETs, as well as organoids, we demonstrate that inhibition of sortilin reduces cellular serotonin concentrations and may therefore serve as a novel therapeutic target to treat patients with carcinoid syndrome.
Keywords:Neuroendocrine Tumors, Functional Syndrome, Carcinoid Syndrome, Serotonin, Sortilin, Organoids, Enteroendocrine Cells, Animals, Mice
Source:Frontiers in Endocrinology
ISSN:1664-2392
Publisher:Frontiers Media SA
Volume:15
Page Range:1331231
Date:17 April 2024
Official Publication:https://doi.org/10.3389/fendo.2024.1331231
PubMed:View item in PubMed

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