In vivo modeling of metastatic human high-grade serous ovarian cancer in mice.
Animals
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Chromosomal Instability
Cystadenocarcinoma, Serous
/ drug therapy
DEAD-box RNA Helicases
/ genetics
DNA Repair
Disease Models, Animal
Drug Resistance, Neoplasm
/ genetics
Drug Screening Assays, Antitumor
/ methods
Feasibility Studies
Female
Humans
Mice
Mice, Knockout
Mutation
Neoplasm Grading
Neoplasm Metastasis
/ genetics
Ovarian Neoplasms
/ drug therapy
PTEN Phosphohydrolase
/ genetics
Peritoneal Neoplasms
/ drug therapy
Primary Cell Culture
Ribonuclease III
/ genetics
Tumor Suppressor Protein p53
/ genetics
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
18
12
2019
accepted:
28
04
2020
revised:
16
06
2020
pubmed:
5
6
2020
medline:
1
9
2020
entrez:
5
6
2020
Statut:
epublish
Résumé
Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies.
Identifiants
pubmed: 32497036
doi: 10.1371/journal.pgen.1008808
pii: PGENETICS-D-19-02029
pmc: PMC7297383
doi:
Substances chimiques
Antineoplastic Agents
0
Trp53 protein, mouse
0
Tumor Suppressor Protein p53
0
Dicer1 protein, mouse
EC 3.1.26.3
Ribonuclease III
EC 3.1.26.3
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
DEAD-box RNA Helicases
EC 3.6.4.13
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
e1008808Subventions
Organisme : NCI NIH HHS
ID : P50 CA217685
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA179137
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218664
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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