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

Felix Bolduan; Alexandra Wetzel; Yvonne Giesecke; Ines Eichhorn; Natalia Alenina; Michael Bader; Thomas E. Willnow; Bertram Wiedenmann; Michael Sigal

doi:10.3389/fendo.2024.1331231

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

Felix Bolduan, Alexandra Wetzel, Yvonne Giesecke, Ines Eichhorn, Natalia Alenina, Michael Bader, Thomas E. Willnow, Bertram Wiedenmann^*, Michael Sigal^*

^*Corresponding author for this work

Department of Biomedicine - Forskning og uddannelse, Skou-bygningen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Article number	1331231
Journal	Frontiers in Endocrinology
Volume	15
ISSN	1664-2392
DOIs	https://doi.org/10.3389/fendo.2024.1331231
Publication status	Published - 2024

Keywords

carcinoid syndrome
enteroendocrine cells
functional syndrome
neuroendocrine tumors
organoids
serotonin
sortilin

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10.3389/fendo.2024.1331231

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title = "Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting",

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 = "carcinoid syndrome, enteroendocrine cells, functional syndrome, neuroendocrine tumors, organoids, serotonin, sortilin",

author = "Felix Bolduan and Alexandra Wetzel and Yvonne Giesecke and Ines Eichhorn and Natalia Alenina and Michael Bader and Willnow, {Thomas E.} and Bertram Wiedenmann and Michael Sigal",

note = "Publisher Copyright: Copyright {\textcopyright} 2024 Bolduan, Wetzel, Giesecke, Eichhorn, Alenina, Bader, Willnow, Wiedenmann and Sigal.",

year = "2024",

doi = "10.3389/fendo.2024.1331231",

language = "English",

volume = "15",

journal = "Frontiers in Endocrinology",

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Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting. / Bolduan, Felix; Wetzel, Alexandra; Giesecke, Yvonne et al.
In: Frontiers in Endocrinology, Vol. 15, 1331231, 2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting

AU - Bolduan, Felix

AU - Wetzel, Alexandra

AU - Giesecke, Yvonne

AU - Eichhorn, Ines

AU - Alenina, Natalia

AU - Bader, Michael

AU - Willnow, Thomas E.

AU - Wiedenmann, Bertram

AU - Sigal, Michael

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - carcinoid syndrome

KW - enteroendocrine cells

KW - functional syndrome

KW - neuroendocrine tumors

KW - organoids

KW - serotonin

KW - sortilin

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DO - 10.3389/fendo.2024.1331231

M3 - Journal article

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AN - SCOPUS:85191867286

SN - 1664-2392

VL - 15

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 1331231

ER -

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

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