Delta-like 3 localizes to neuroendocrine cells and plays a pivotal role in gastrointestinal neuroendocrine malignancy.
Aged
Apoptosis
Carcinoma, Neuroendocrine
/ genetics
Cell Line, Tumor
Gastrointestinal Neoplasms
/ genetics
Gastrointestinal Tract
/ cytology
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Membrane Proteins
/ genetics
Neuroendocrine Cells
/ metabolism
Up-Regulation
DLL3
apoptosis
chromogranin A
neuroendocrine
neuroendocrine carcinoma
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
02
04
2019
revised:
23
07
2019
accepted:
31
07
2019
pubmed:
2
8
2019
medline:
12
10
2019
entrez:
2
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31369178
doi: 10.1111/cas.14157
pmc: PMC6778628
doi:
Substances chimiques
DLL3 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3122-3131Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP 18K16375
Organisme : Osaka Medical College (OMC) Internal Research Grant
Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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