PDF(Pubmed)
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.
摘要：
神经内分泌肿瘤（NETs）的一个子集可以导致激素的过度分泌，神经肽，和生物胺进入血液。这些所谓的功能性NETs引发激素相关疾病，并导致几种不同的综合征，取决于释放的因素。最常见的功能综合征之一，类癌综合征,主要表现为5-羟色胺的过度分泌。然而,在分子水平上区分功能性肿瘤和非功能性肿瘤的原因尚不清楚。这里,我们证明了sortilin的表达，一种广泛表达的跨膜受体，参与细胞内蛋白质分选，与非功能性NETs相比,功能性显著增加,因此可用作功能性NETs的生物标志物。此外，使用功能性NET的细胞系模型，以及类器官，我们证明，抑制sortilin可降低细胞5-羟色胺浓度，因此可作为治疗类癌综合征患者的新治疗靶点。
