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Item Type: | Article |
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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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