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Delta-like 3 定位于神经内分泌细胞，在胃肠道神经内分泌恶性肿瘤中发挥关键作用。

Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.

机构信息

Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki, Japan.

Translational Research Program, Osaka Medical College, Takatsuki, Japan.

出版信息

Cancer Sci. 2019 Oct;110(10):3122-3131. doi: 10.1111/cas.14157. Epub 2019 Aug 14.

DOI:10.1111/cas.14157
PMID:31369178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6778628/
Abstract

Delta-like 3 (DLL3) is a member of the Delta/Serrate/Lag2 (DSL) group of Notch receptor ligands. Five DSL ligands are known in mammals, among which DLL3 has a unique structure. In the last few years, DLL3 has attracted attention as a novel molecular targeting gene in neuroendocrine carcinoma of the lung due to its high expression. However, the expression pattern and functions of DLL3 in the gastrointestinal tract and gastrointestinal neuroendocrine carcinoma remain unclear. In this study, we examined the expression and role of DLL3 in the gastrointestinal tract, as well as in gastrointestinal neuroendocrine carcinoma. Immunohistochemical staining of the human normal gastrointestinal tract revealed that DLL3 localized in neuroendocrine cells. DLL3 showed intense staining in chromogranin A-positive gastric cancer specimens. Real-time quantitative RT-PCR and western blotting analyses showed considerable upregulation of DLL3 in gastrointestinal neuroendocrine carcinoma cell lines. Immuno-electron microscopy demonstrated abundant expression of DLL3 in neurosecretory granules in these cells. Furthermore, gene silencing of DLL3 caused significant growth inhibition through the induction of intrinsic apoptosis. Our findings suggest that DLL3 is expressed in neuroendocrine cells of the gastrointestinal tract and that it has a pivotal role in gastrointestinal neuroendocrine carcinoma cells. Based on these findings, further investigations are required to achieve a breakthrough in developing therapeutic strategies for gastrointestinal neuroendocrine carcinoma.

摘要

Delta-like 3（DLL3）是 Notch 受体配体 Delta/Serrate/Lag2（DSL）家族的成员之一。哺乳动物中已知有 5 种 DSL 配体，其中 DLL3 具有独特的结构。在过去的几年中，由于 DLL3 在肺神经内分泌癌中的高表达，它作为一种新型的分子靶向基因引起了关注。然而，DLL3 在胃肠道和胃肠道神经内分泌癌中的表达模式和功能仍不清楚。在本研究中，我们研究了 DLL3 在胃肠道以及胃肠道神经内分泌癌中的表达和作用。免疫组织化学染色显示 DLL3 定位于神经内分泌细胞。在胃 chromogranin A 阳性的癌标本中，DLL3 表现出强烈的染色。实时定量 RT-PCR 和 Western blot 分析显示，胃肠道神经内分泌癌细胞系中 DLL3 的表达显著上调。免疫电子显微镜显示这些细胞中的神经分泌颗粒中大量表达 DLL3。此外，通过诱导内在凋亡，DLL3 的基因沉默导致显著的生长抑制。我们的研究结果表明，DLL3 在胃肠道的神经内分泌细胞中表达，并在胃肠道神经内分泌癌细胞中发挥关键作用。基于这些发现，需要进一步研究以在开发胃肠道神经内分泌癌的治疗策略方面取得突破。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b3/6778628/d895a65ac547/CAS-110-3122-g008.jpg
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Rovalpituzumab Tesirine: A Novel DLL3-Targeting Antibody-Drug Conjugate.
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