In vivo modeling of metastatic human high-grade serous ovarian cancer in mice

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 ty...

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Bibliographic Details
Published in:PLoS Genetics 2020, Vol.16 (6)
Main Authors: Kim, Olga, Park, Eun Young, Klinkebiel, David L, Pack, Svetlana D, Shin, Yong-Hyun, Abdullaev, Zied, Emerson, Robert E, Coffey, Donna M, Kwon, Sun Young, Creighton, Chad J, Kwon, Sanghoon, Chang, Edmund C, Chiang, Theodore, Yatsenko, Alexander N, Chien, Jeremy, Cheon, Dong-Joo, Yang-Hartwich, Yang, Nakshatri, Harikrishna, Nephew, Kenneth P, Behringer, Richard R, Fernández, Facundo M, Cho, Chi-Heum, Vanderhyden, Barbara, Drapkin, Ronny, Bast, Robert C, Miller, Kathy D, Karpf, Adam R, Kim, Jaeyeon
Format: Report
Language:English
Subjects:
Animal research models
Cancer metastasis
Genetic aspects
Genetic engineering
Methods
Ovarian cancer
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Summary: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.
ISSN:1553-7390
DOI:10.1371/journal.pgen.1008808