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Updated: May 5, 2026
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables
Felix Bolduan1,2, Alexandra Wetzel1, Yvonne Giesecke1
1Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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.
Insights
Sortilin expression is elevated in functional neuroendocrine tumors (NETs), distinguishing them from non-functional NETs. Inhibiting sortilin may offer a new treatment for carcinoid syndrome by reducing serotonin levels.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Functional neuroendocrine tumors (NETs) over-secrete hormones, leading to distinct clinical syndromes.
- Carcinoid syndrome, a common functional NET syndrome, involves excessive serotonin secretion.
- Molecular differences between functional and non-functional NETs are not well understood.
Purpose of the Study:
- To identify molecular distinctions between functional and non-functional NETs.
- To evaluate sortilin as a potential biomarker for functional NETs.
- To investigate sortilin as a therapeutic target for carcinoid syndrome.
Main Methods:
- Comparative analysis of sortilin expression in functional versus non-functional NETs.
- Utilizing a cell line model of functional NETs.
- Employing organoid models for therapeutic target validation.
Main Results:
- Sortilin expression is significantly increased in functional NETs compared to non-functional NETs.
- Sortilin can serve as a biomarker to differentiate functional NETs.
- Inhibition of sortilin decreases cellular serotonin concentrations in functional NET models.
Conclusions:
- Sortilin is a potential biomarker for identifying functional NETs.
- Targeting sortilin presents a novel therapeutic strategy for carcinoid syndrome by modulating serotonin levels.
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