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.

Figure 1

Development of ovarian tumors following injection of ES-2 ovarian cancer cells under the bursal membrane of nude mouse ovaries. Left figure- Proliferating cancer cells invade the normal tissue and increase the ovarian mass to diameters > 10-fold in size (indicated by arrows). Right figure- A single follicle containing a growing oocyte, indicated by an arrow, is clearly visible in the mass of tumor tissue.

Figure 2

Morphology of the ovarian surface epithelium in wild-type (A; 12 months), Sl^d heterozygous (B, C; 12 months) and homozygous (D; 6 months) mice. Ovaries from wild-type mice contain developing follicles and a covering layer of columnar OSE. In 12-month-old Sl^d heterozygous mice, there is a depletion of follicles, and the ovarian surface has become very convoluted (B), with this papillary surface sometimes leading to deep invaginations, as indicated by the arrow (C). By 6 months of age, the ovaries of homozygous Sl^d mice are completely abnormal, with no recognizable ovarian structures, and are composed primarily of invasive epithelial tubules. (E) Human ovarian papillomatosis, for comparison.