In vivo modeling of metastatic human highgrade serous ovarian cancer in mice

Olga Kim, Eun Young Park, David L. Klinkebie, Svetlana D. Pack, Yong Hyun Shin, Zied Abdullaev, Robert E. Emerson, Donna M. Coffey, Sun Young Kwon, Chad J. Creighton, Sanghoon Kwon, Edmund C. Chang, Theodore Chiang, Alexander N. Yatsenko, Jeremy Chien, Dong Joo Cheon, Yang Yang-Hartwich, Harikrishna Nakshatri, Kenneth P. Nephew, Richard R. BehringerFacundo M. Fernandez, Chi Heum Cho, Barbara Vanderhyden, Ronny Drapkin, Robert C. Bast, Kathy D. Miller, Adam R. Karpf, Jaeyeon Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere1008808
JournalPLoS genetics
Volume16
Issue number6
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Kim, O., Park, E. Y., Klinkebie, D. L., Pack, S. D., Shin, Y. H., Abdullaev, Z., Emerson, R. E., Coffey, D. M., Kwon, S. Y., Creighton, C. J., Kwon, S., Chang, E. C., Chiang, T., Yatsenko, A. N., Chien, J., Cheon, D. J., Yang-Hartwich, Y., Nakshatri, H., Nephew, K. P., ... Kim, J. (2020). In vivo modeling of metastatic human highgrade serous ovarian cancer in mice. PLoS genetics, 16(6), [e1008808]. https://doi.org/10.1371/journal.pgen.1008808