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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| Veröffentlicht in: | PLoS genetics 2020-06, Vol.16 (6), p.e1008808-e1008808 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1371/journal.pgen.1008808 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1008808</identifier><identifier>PMID: 32497036</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Animal models ; Animal research models ; Ascites ; Biochemistry ; Biology and Life Sciences ; Cancer metastasis ; DNA repair ; Fallopian tube ; Fallopian tubes ; Funding ; Genetic aspects ; Genetic engineering ; Genital cancers ; Genomes ; Genomic instability ; Gynecological cancer ; Gynecology ; Hemorrhage ; Laboratories ; Medical prognosis ; Medical research ; Medicine ; Medicine and Health Sciences ; Metastases ; Metastasis ; Methods ; Molecular biology ; Mutation ; Obstetrics ; Ovarian cancer ; p53 Protein ; Pathology ; Peritoneum ; PTEN protein ; R&D ; Research & development ; Research and Analysis Methods ; Tumors</subject><ispartof>PLoS genetics, 2020-06, Vol.16 (6), p.e1008808-e1008808</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 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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.</description><subject>Animal models</subject><subject>Animal research models</subject><subject>Ascites</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Cancer metastasis</subject><subject>DNA repair</subject><subject>Fallopian tube</subject><subject>Fallopian tubes</subject><subject>Funding</subject><subject>Genetic aspects</subject><subject>Genetic engineering</subject><subject>Genital cancers</subject><subject>Genomes</subject><subject>Genomic instability</subject><subject>Gynecological cancer</subject><subject>Gynecology</subject><subject>Hemorrhage</subject><subject>Laboratories</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Molecular biology</subject><subject>Mutation</subject><subject>Obstetrics</subject><subject>Ovarian cancer</subject><subject>p53 Protein</subject><subject>Pathology</subject><subject>Peritoneum</subject><subject>PTEN protein</subject><subject>R&D</subject><subject>Research & development</subject><subject>Research and Analysis 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vivo modeling of metastatic human high-grade serous ovarian cancer in mice</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c633t-4a00d67f5e173693bb958bfd27491d73451e21ea070299bef77a24243dd0cd453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animal research 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Barbara</au><au>Drapkin, Ronny</au><au>Bast, Robert C</au><au>Miller, Kathy D</au><au>Karpf, Adam R</au><au>Kim, Jaeyeon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo modeling of metastatic human high-grade serous ovarian cancer in mice</atitle><jtitle>PLoS genetics</jtitle><date>2020-06-04</date><risdate>2020</risdate><volume>16</volume><issue>6</issue><spage>e1008808</spage><epage>e1008808</epage><pages>e1008808-e1008808</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><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.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32497036</pmid><doi>10.1371/journal.pgen.1008808</doi><orcidid>https://orcid.org/0000-0002-1030-8565</orcidid><orcidid>https://orcid.org/0000-0003-1815-5548</orcidid><orcidid>https://orcid.org/0000-0002-0437-4099</orcidid><orcidid>https://orcid.org/0000-0002-6912-6977</orcidid><orcidid>https://orcid.org/0000-0002-0866-0666</orcidid><orcidid>https://orcid.org/0000-0001-8159-539X</orcidid><orcidid>https://orcid.org/0000-0003-2811-8281</orcidid><orcidid>https://orcid.org/0000-0001-9963-8909</orcidid><orcidid>https://orcid.org/0000-0001-8876-0052</orcidid><orcidid>https://orcid.org/0000-0002-8410-0185</orcidid><orcidid>https://orcid.org/0000-0003-4744-8374</orcidid><orcidid>https://orcid.org/0000-0002-6090-703X</orcidid><orcidid>https://orcid.org/0000-0003-3256-6626</orcidid><orcidid>https://orcid.org/0000-0002-6134-4902</orcidid><orcidid>https://orcid.org/0000-0002-3089-0636</orcidid><orcidid>https://orcid.org/0000-0002-7644-7189</orcidid><orcidid>https://orcid.org/0000-0001-6345-2088</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2020-06, Vol.16 (6), p.e1008808-e1008808 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_plos_journals_2424468841 |
| source | Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animal models Animal research models Ascites Biochemistry Biology and Life Sciences Cancer metastasis DNA repair Fallopian tube Fallopian tubes Funding Genetic aspects Genetic engineering Genital cancers Genomes Genomic instability Gynecological cancer Gynecology Hemorrhage Laboratories Medical prognosis Medical research Medicine Medicine and Health Sciences Metastases Metastasis Methods Molecular biology Mutation Obstetrics Ovarian cancer p53 Protein Pathology Peritoneum PTEN protein R&D Research & development Research and Analysis Methods Tumors |
| title | In vivo modeling of metastatic human high-grade serous ovarian cancer in mice |
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