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

• DOI: 10.1371/journal.pgen.1008808
• Publication Date: 2020-06-04T17:53:54Z
• Authors: Olga Kim; Eun Young Park; David L. Klinkebiel; 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. Yats...; Jeremy Chien; Dong-Joo Cheon; Yang Yang-Hartwich; Harikrishna Naksh...; Kenneth P. Nephew; Richard R. Behringer; Facundo M. Fernández; Chi-Heum Cho; Barbara Vanderhyden; Ronny Drapkin; Robert C. Bast; Kathy D. Miller; Adam R. Karpf; Jaeyeon Kim
• Keywords: Serous carcinoma; Peritoneal cavity

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model metastasis in vivo. Here we describe mouse models high-grade serous ovarian cancer, also known as carcinoma (HGSC), the most common and deadliest type. Mice genetically engineered harbor Dicer1 Pten inactivation mutant p53 robustly replicate peritoneal metastases HGSC with complete penetrance. Arising from fallopian tube, tumors spread ovary metastasize throughout pelvic cavities, invariably inducing hemorrhagic ascites. Widespread abundant ultimately cause deaths (100%). Besides phenotypic histopathological similarities, HGSCs display marked chromosomal instability, impaired DNA repair, chemosensitivity. Faithfully recapitulating clinical well molecular genomic features HGSC, this murine will be valuable elucidating mechanisms underlying development progression metastatic evaluating potential therapies.