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

English version

Autoři: Olga Kim ^aff001; Eun Young Park ^aff001; David L. Klinkebiel ^aff002; Svetlana D. Pack ^aff003; Yong-Hyun Shin ^aff001; Zied Abdullaev ^aff003; Robert E. Emerson ^aff004; Donna M. Coffey ^aff005; Sun Young Kwon ^aff006; Chad J. Creighton ^aff007; Sanghoon Kwon ^aff008; Edmund C. Chang ^aff009; Theodore Chiang ^aff009; Alexander N. Yatsenko ^aff010; Jeremy Chien ^aff011; Dong-Joo Cheon ^aff012; Yang Yang-Hartwich ^aff013; Harikrishna Nakshatri ^aff014; Kenneth P. Nephew ^aff015; Richard R. Behringer ^aff016; Facundo M. Fernández ^aff017; Chi-Heum Cho ^aff018; Barbara Vanderhyden ^aff019; Ronny Drapkin ^aff020; Robert C. Bast, Jr ^aff021; Kathy D. Miller ^aff022; Adam R. Karpf ^aff023; Jaeyeon Kim ^aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ^aff001; Department of Biochemistry and Molecular Biology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America ^aff002; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America ^aff003; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ^aff004; Department of Pathology and Genomic Medicine, Houston Methodist and Weill Cornell Medical College, Houston, Texas, United States of America ^aff005; Department of Pathology, School of Medicine, Keimyung University, Daegu, Republic of Korea ^aff006; Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America ^aff007; Research and Development Center, Bioway Inc, Seoul, Republic of Korea ^aff008; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America ^aff009; Department of Obstetrics, Gynecology & Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ^aff010; Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, California, United States of America ^aff011; Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY, United States of America ^aff012; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United States of America ^aff013; Department of Surgery, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ^aff014; Medical Sciences Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Bloomington, Indiana, United States of America ^aff015; Departments of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ^aff016; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, United States of America ^aff017; Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu, Republic of Korea ^aff018; Department of Cellular and Molecular Medicine, University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada ^aff019; Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America ^aff020; Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America ^aff021; Department of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine Indianapolis, Indiana, United States of America ^aff022; Eppley Institute for Cancer Research, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America ^aff023
Vyšlo v časopise: In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008808
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008808

Souhrn

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.

Klíčová slova:

Animal models of disease – Chromosomes – Mammalian genomics – Metastasis – Metastatic tumors – Mouse models – Ovarian cancer – Fallopian tubes

Zdroje

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Článek Transcriptomic stratification of late-onset Alzheimer's cases reveals novel genetic modifiers of disease pathology

Článek Identification of Clec4b as a novel regulator of bystander activation of auto-reactive T cells and autoimmune disease

Článek Genetic analysis of osteoblast activity identifies Zbtb40 as a regulator of osteoblast activity and bone mass

Článek Adaptation of codon usage to tRNA I34 modification controls translation kinetics and proteome landscape

Článek Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

Článek Duplication and divergence of the retrovirus restriction gene Fv1 in Mus caroli allows protection from multiple retroviruses

Článek JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage

Článek Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase

Článek Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis

Článek Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade