Sortilin: A novel marker and potential therapeutic target for functional neuroendocrine tumors

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Introduction: A subset of neuroendocrine tumors (NETs) causes a hormone-related disease (functional syndrome); e.g. carcinoid syndrome due to over-secretion of mainly serotonin. Notably, on a molecular level, what distinguishes this subset of functional NETs from nonfunctional tumors is unknown. Furthermore, accurate models of functional NETs are missing. Sortilin, a widely expressed transmembrane receptor, is expressed in many cancer cells, including NETs, and is involved in secretion processes.

Aim(s): To explore the role of sortilin in functional NETs and the use of neuroendocrine differentiated organoids as a model of the functional syndrome.

Materials and methods: Tissue from functional and non-functional NETs was immunohistochemically analyzed for sortilin expression. Sortilin was inhibited by using a small molecule inhibitor in a cell culture model of NETs (BON cells) and serotonin content was estimated by high-performance liquid chromatography (HPLC). Murine organoids were treated with NOTCH and EGF signaling pathway inhibitors to enrich neuroendocrine cells. HPLC measured the serotonin content of these neuroendocrine organoids with and without sortilin inhibition.

Conference:

Presenting Author: Bolduan F

Authors: Bolduan F, Wetzel A, Giesecke Y, Eichhorn I, Alenina N,

Keywords: Neuroendocrine tumor, Functional syndrome, Carcinoid syndrome, Serotonin, Sortilin, Organoids, Enteroendocrine cells,