
In vivo modeling of metastatic human high-grade serous ovarian cancer in mice
Author(s) -
Olga Kim,
Eun Young Park,
David Klinkebiel,
Svetlana Pack,
Yong-Hyun Shin,
Zied Abdullaev,
Robert E. Emerson,
Donna Coffey,
Sun Young Kwon,
Chad J. Creighton,
Sang-Hoon Kwon,
Edmond ChinPing Chang,
Theodore Chiang,
Alexander N. Yatsenko,
Jeremy Chien,
DongJoo Cheon,
Yang Yang-Hartwich,
Harikrishkshatri,
Kenneth P. Nephew,
Richard R. Behringer,
Facundo M. Fernández,
Chi-Heum Cho,
Barbara C. Vanderhyden,
Ronny Drapkin,
Robert C. Bast,
Kathy D. Miller,
Adam R. Karpf,
Jaeyeon Kim
Publication year - 2020
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1008808
Subject(s) - ovarian cancer , biology , metastasis , cancer research , serous fluid , cancer , serous carcinoma , ovarian carcinoma , ovary , pten , peritoneal cavity , pathology , pi3k/akt/mtor pathway , medicine , genetics , signal transduction , biochemistry , anatomy
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.