Pattern of Invasion in Human Pancreatic Cancer Organoids Is Associated with Loss of SMAD4 and Clinical Outcome.
Adenocarcinoma
/ metabolism
Biomarkers, Tumor
/ genetics
Carcinoma, Pancreatic Ductal
/ metabolism
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Invasiveness
Organoids
/ metabolism
Pancreatic Neoplasms
/ metabolism
Prognosis
Signal Transduction
Smad4 Protein
/ genetics
Survival Rate
Tumor Cells, Cultured
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
14
05
2019
revised:
24
01
2020
accepted:
01
05
2020
pubmed:
8
5
2020
medline:
18
11
2020
entrez:
8
5
2020
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal and collective. Each individual PDAC gave rise to organoids with a predominant phenotype, and PDAC that generated organoids with predominantly mesenchymal invasion showed a worse prognosis. Collective invasion predominated in organoids from cancers with somatic mutations in the driver gene
Identifiants
pubmed: 32376602
pii: 0008-5472.CAN-19-1523
doi: 10.1158/0008-5472.CAN-19-1523
pmc: PMC7335355
mid: NIHMS1592760
doi:
Substances chimiques
Biomarkers, Tumor
0
SMAD4 protein, human
0
Smad4 Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2804-2817Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK107781
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217846
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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