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Characteristics of in Vivo Model Systems for Ovarian Cancer Studies.
Tudrej P
,
Kujawa KA
,
Cortez AJ
,
Lisowska KM
.
Abstract
An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.
Figure 1.
(A) Schematic diagram of reproductive system of Drosophila melanogaster. (B) Migration of border cells in the developing ovarian follicle. GSC—germline stem cell, FSC—follicle stem cell, aPC—anterior polar cell, pPC—posterior polar cell, BC—border cell, FC—follicle cell, NC—nurse cell.
Figure 2.
Mouse model designed by Orsulic et al. [67] to evaluate oncogenes necessary for neoplastic transformation of ovarian surface epithelium (OSE) cells with an inactive p53 gene. TVA, tumor virus receptor A.
Figure 3.
Mouse model used by Flesken-Nikitin et al. [71] for specific knock-out of p53 and pRb genes in OSE cells.
Figure 4.
Mouse model used by Perets et al. [73] for the tissue-specific knock-out of the p53 and Brca1 genes, using Cre recombinase, the expression of which was limited to the Müllerian epithelia and induced after administration of the tetracycline.
Aleksandrowicz,
Ethical euthanasia and short-term anesthesia of the chick embryo.
2015, Pubmed
Aleksandrowicz,
Ethical euthanasia and short-term anesthesia of the chick embryo.
2015,
Pubmed
Anzick,
AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer.
1997,
Pubmed
Bai,
Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer.
2001,
Pubmed
Barua,
Histopathology of ovarian tumors in laying hens: a preclinical model of human ovarian cancer.
2009,
Pubmed
Beaufort,
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
2016,
Pubmed
Beccari,
The JAK/STAT pathway is required for border cell migration during Drosophila oogenesis.
2002,
Pubmed
Ben-David,
Patient-derived xenografts undergo mouse-specific tumor evolution.
2017,
Pubmed
Beral,
Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.
2015,
Pubmed
Bernardo,
Advantages of the avian model for human ovarian cancer.
2018,
Pubmed
Bobbs,
Emerging and Evolving Ovarian Cancer Animal Models.
2015,
Pubmed
Cai,
Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells.
2015,
Pubmed
Chen,
VEGF, VEGFRs expressions and activated STATs in ovarian epithelial carcinoma.
2004,
Pubmed
Cheng,
Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract.
2005,
Pubmed
Chuffa,
The role of sex hormones and steroid receptors on female reproductive cancers.
2017,
Pubmed
Clark-Knowles,
Conditional inactivation of Brca1, p53 and Rb in mouse ovaries results in the development of leiomyosarcomas.
2010,
Pubmed
Connolly,
Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer.
2003,
Pubmed
Cortez,
Advances in ovarian cancer therapy.
2019,
Pubmed
Cybulska,
A Genomically Characterized Collection of High-Grade Serous Ovarian Cancer Xenografts for Preclinical Testing.
2019,
Pubmed
DeBord,
The chick chorioallantoic membrane (CAM) as a versatile patient-derived xenograft (PDX) platform for precision medicine and preclinical research.
2018,
Pubmed
Dinulescu,
Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer.
2005,
Pubmed
Domanitskaya,
Phantom, a cytochrome P450 enzyme essential for ecdysone biosynthesis, plays a critical role in the control of border cell migration in Drosophila.
2014,
Pubmed
Domcke,
Evaluating cell lines as tumour models by comparison of genomic profiles.
2014,
Pubmed
Dubeau,
The cell of origin of ovarian epithelial tumours.
2008,
Pubmed
Fader,
Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: Reducing overtreatment without compromising survival?
2017,
Pubmed
Fan,
Cell type-specific targeted mutations of Kras and Pten document proliferation arrest in granulosa cells versus oncogenic insult to ovarian surface epithelial cells.
2009,
Pubmed
Flesken-Nikitin,
Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.
2013,
Pubmed
Flesken-Nikitin,
Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium.
2003,
Pubmed
Fong,
Ovarian cancer mouse models: a summary of current models and their limitations.
2011,
Pubmed
Garson,
Models of ovarian cancer--are we there yet?
2005,
Pubmed
Ghiglione,
The Drosophila cytokine receptor Domeless controls border cell migration and epithelial polarization during oogenesis.
2003,
Pubmed
Goyos,
Tumorigenesis and anti-tumor immune responses in Xenopus.
2009,
Pubmed
,
Xenbase
Hall,
Hippo pathway effector Yap is an ovarian cancer oncogene.
2010,
Pubmed
Hamilton,
Experimental model systems of ovarian cancer: applications to the design and evaluation of new treatment approaches.
1984,
Pubmed
Hardwick,
An oncologist׳s friend: How Xenopus contributes to cancer research.
2016,
Pubmed
,
Xenbase
Harris,
Targeting HER2 in patient-derived xenograft ovarian cancer models sensitizes tumors to chemotherapy.
2019,
Pubmed
Hawkridge,
The chicken model of spontaneous ovarian cancer.
2015,
Pubmed
Hernandez,
Characterization of ovarian cancer cell lines as in vivo models for preclinical studies.
2017,
Pubmed
House,
Recent technological advances in using mouse models to study ovarian cancer.
2014,
Pubmed
Johnson,
The hen as a model of ovarian cancer.
2013,
Pubmed
Kamat,
Metronomic chemotherapy enhances the efficacy of antivascular therapy in ovarian cancer.
2007,
Pubmed
Karnezis,
Preclinical Models of Ovarian Cancer: Pathogenesis, Problems, and Implications for Prevention.
2018,
Pubmed
Kim,
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
2012,
Pubmed
Kim,
The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.
2015,
Pubmed
King,
Evaluating the progenitor cells of ovarian cancer: analysis of current animal models.
2011,
Pubmed
Klovstad,
Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint.
2008,
Pubmed
Kolfschoten,
Development of a panel of 15 human ovarian cancer xenografts for drug screening and determination of the role of the glutathione detoxification system.
2000,
Pubmed
Konstantinopoulos,
Current status and evolution of preclinical drug development models of epithelial ovarian cancer.
2014,
Pubmed
Kujawa,
[Ovarian cancer--from biology to clinic].
2016,
Pubmed
Kurman,
The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory.
2010,
Pubmed
Li,
Polycomb group genes Psc and Su(z)2 restrict follicle stem cell self-renewal and extrusion by controlling canonical and noncanonical Wnt signaling.
2010,
Pubmed
Lin,
The Hippo pathway controls border cell migration through distinct mechanisms in outer border cells and polar cells of the Drosophila ovary.
2015,
Pubmed
Liu,
Gene expression differences between matched pairs of ovarian cancer patient tumors and patient-derived xenografts.
2019,
Pubmed
Lokman,
Chick chorioallantoic membrane (CAM) assay as an in vivo model to study the effect of newly identified molecules on ovarian cancer invasion and metastasis.
2015,
Pubmed
Lucas,
The Hippo pathway polarizes the actin cytoskeleton during collective migration of Drosophila border cells.
2013,
Pubmed
Létourneau,
Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer.
2013,
Pubmed
Mabuchi,
RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer.
2007,
Pubmed
Magnotti,
The latest animal models of ovarian cancer for novel drug discovery.
2019,
Pubmed
Maru,
Current Status of Patient-Derived Ovarian Cancer Models.
2019,
Pubmed
McCloskey,
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
2014,
Pubmed
McCloskey,
Ovarian Cancer Immunotherapy: Preclinical Models and Emerging Therapeutics.
2018,
Pubmed
Miyoshi,
Mouse transgenic for murine oviduct-specific glycoprotein promoter-driven simian virus 40 large T-antigen: tumor formation and its hormonal regulation.
2003,
Pubmed
Modugno,
Hormone response in ovarian cancer: time to reconsider as a clinical target?
2013,
Pubmed
Molthoff,
Human ovarian cancer xenografts in nude mice: characterization and analysis of antigen expression.
1991,
Pubmed
Montell,
Group choreography: mechanisms orchestrating the collective movement of border cells.
2012,
Pubmed
Mullany,
Molecular and functional characteristics of ovarian surface epithelial cells transformed by KrasG12D and loss of Pten in a mouse model in vivo.
2011,
Pubmed
Mullany,
Minireview: animal models and mechanisms of ovarian cancer development.
2012,
Pubmed
Naora,
Ovarian cancer metastasis: integrating insights from disparate model organisms.
2005,
Pubmed
Orsulic,
Induction of ovarian cancer by defined multiple genetic changes in a mouse model system.
2002,
Pubmed
POLACK,
The xenopus pregnancy test.
2007,
Pubmed
,
Xenbase
Pan,
The hippo signaling pathway in development and cancer.
2010,
Pubmed
Perets,
Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models.
2014,
Pubmed
Quinn,
Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53.
2010,
Pubmed
Ren,
Mutant p53 Promotes Epithelial Ovarian Cancer by Regulating Tumor Differentiation, Metastasis, and Responsiveness to Steroid Hormones.
2017,
Pubmed
Ribatti,
Chick embryo chorioallantoic membrane as a useful tool to study angiogenesis.
2009,
Pubmed
Ribatti,
The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model.
2017,
Pubmed
Rosales-Nieves,
Genetics and mechanisms of ovarian cancer: parallels between Drosophila and humans.
2015,
Pubmed
Shaw,
Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer.
2005,
Pubmed
Sherman-Baust,
A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development.
2014,
Pubmed
Silver,
Requirement for JAK/STAT signaling throughout border cell migration in Drosophila.
2005,
Pubmed
Silver,
Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila.
2002,
Pubmed
Snigdha,
Hippo Signaling in Cancer: Lessons From Drosophila Models.
2019,
Pubmed
Stanley,
Endocrine treatment of high grade serous ovarian carcinoma; quantification of efficacy and identification of response predictors.
2019,
Pubmed
Szabova,
Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.
2012,
Pubmed
Tandon,
Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling.
2017,
Pubmed
,
Xenbase
Tanner,
Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer.
2000,
Pubmed
Tanwar,
Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer.
2014,
Pubmed
Thaker,
Antivascular therapy for orthotopic human ovarian carcinoma through blockade of the vascular endothelial growth factor and epidermal growth factor receptors.
2005,
Pubmed
Tirodkar,
MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location.
2015,
Pubmed
Torres-Arzayus,
High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene.
2004,
Pubmed
Treviño,
Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin?
2011,
Pubmed
Tudrej,
Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8.
2018,
Pubmed
Vu,
Chick chorioallantoic membrane assay as an in vivo model to study the effect of nanoparticle-based anticancer drugs in ovarian cancer.
2019,
Pubmed
Walsh,
Humanized Mouse Models of Clinical Disease.
2017,
Pubmed
Wu,
Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways.
2007,
Pubmed
Wu,
Impact of oviductal versus ovarian epithelial cell of origin on ovarian endometrioid carcinoma phenotype in the mouse.
2017,
Pubmed
Xi,
A gradient of JAK pathway activity patterns the anterior-posterior axis of the follicular epithelium.
2003,
Pubmed
Xing,
A mouse model for the molecular characterization of brca1-associated ovarian carcinoma.
2006,
Pubmed
Xing,
A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance.
2005,
Pubmed
Zhang,
The Hippo pathway transcriptional co-activator, YAP, is an ovarian cancer oncogene.
2011,
Pubmed
Zietarska,
Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC).
2007,
Pubmed
