Animal models of ovarian cancer

Abstract

Ovarian cancer is the most lethal of all of the gynecological cancers and can arise from any cell type of the ovary, including germ cells, granulosa or stromal cells. However, the majority of ovarian cancers arise from the surface epithelium, a single layer of cells that covers the surface of the ovary. The lack of a reliable and specific method for the early detection of epithelial ovarian cancer results in diagnosis occurring most commonly at late clinical stages, when treatment is less effective. In part, the deficiency in diagnostic tools is due to the lack of markers for the detection of preneoplastic or early neoplastic changes in the epithelial cells, which reflects our rather poor understanding of this process. Animal models which accurately represent the cellular and molecular changes associated with the initiation and progression of human ovarian cancer have significant potential to facilitate the development of better methods for the early detection and treatment of ovarian cancer. This review describes some of the experimental animal models of ovarian tumorigenesis that have been reported, including those involving specific reproductive factors and environmental toxins. Consideration has also been given to the recent progress in modeling ovarian cancer using genetically engineered mice.

Immune Cells in the Normal Ovary and Spontaneous Ovarian Tumors in the Laying Hen (Gallus domesticus) Model of Human Ovarian Cancer

“…There are a number of rodent models of ovarian cancer based on genetically engineered or chemically induced tumors or on implantation of human tumors in SCID (Severe Combined Immunodeficiency) or RAG (Recombination activating gene) deficient mice [8]. However, most rodent models do not develop ovarian cancer spontaneously and those that do often produce only one histotype [8], [9], [10], [11], [12].…”

“…However, most rodent models do not develop ovarian cancer spontaneously and those that do often produce only one histotype [8], [9], [10], [11], [12]. While these models are useful for insights into genetic and environmental factors contributing to cancers and to development of chemo-therapeutic strategies, they are less appropriate for investigation of early spontaneous events related to tumor immunology because it is not clear if they undergo the same natural or spontaneous events that lead to ovarian tumors.…”

Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology

“…The phenotypes observed in the Pcsk6 tm1Rob ovaries are unlike many other single gene knockout or transgenic models described (Matzuk & Lamb 2002, Vanderhyden et al 2003. Reduced oocyte number or accelerated oocyte loss is a precursor to pathologies observed in different mouse models (Matzuk & Lamb 2002, Vanderhyden et al 2003, Vanderhyden 2005.…”

“…Reduced oocyte number or accelerated oocyte loss is a precursor to pathologies observed in different mouse models (Matzuk & Lamb 2002, Vanderhyden et al 2003, Vanderhyden 2005. In general, ovarian follicle depletion is associated with increased epithelial invaginations and inclusion cysts, as well as with formation of tubular adenomas.…”

“…In general, ovarian follicle depletion is associated with increased epithelial invaginations and inclusion cysts, as well as with formation of tubular adenomas. Invasive epithelial tubules and tubulostromal adenomas develop in the vast majority of mice with germ cell deficiencies, such as those produced by mutations in the W (Kit) or Sl (Kitl) loci (Murphy 1972, Murphy & Beamer 1973, Ishimura et al 1986, Vanderhyden et al 2003. These abnormalities typically form by 7 mo and are directly correlated with oocyte depletion.…”