We established a reproducible murine xenograft model of ovarian carcinoma employing tumor cells harvested from the ascites of an ovarian cancer patient, where the cells may be reproducibly maintained and directly passaged to subsequent hosts. This model requires no selective methods before intraperitoneal growth such as enzymatic digestion, selective anchorage-independent growth, and subcutaneous inoculation [7, 12, 15, 16]. As a result, the unwanted implications of the manipulations were avoided.
The tumor cells from the ascites were hyperchromatic for CA125 antigen, Pan-cytokcratin and epithelial antigen, which confirmed it to be epithelial differentiation . MMP-2 is believed to be involved in two aspects of the ovarian cancer spread process: It helps tumor cells penetrate the basement membrane of the ovary to invade the stroma , and may enable the tumor cells to detach from the epithelial surface and migrate into the peritoneal cavity [22, 23]. It is reported that the rate of MMP2 expression in ovarian cancer is high and irrelevant with either clinical staging or histological typing . One possible explanation was the grave malignance of ovarian cancer. In our model, we also noted tumor cells with high MMP-2 expression. P53 mutation occurs early in the progression of ovarian cancer , which is found in some 50% or more of advanced serous adenocarcinomas while rarely noted in earlier stages [26–28]. In this model, tumor cells show intense expression of p53, consistent with the previous reports.
We examined the transplanted tumors in ascites at different passages, and found that the characteristics did not change from one generation to another. As a result, this may offer an unlimited in vivo supply of stable tumor cells, which may be of great value for ensuring reproducibility and reliability of research results. In the future, we may establish similar models of other ovarian cancer subtypes for furthering our knowledge on the disease.
In this model, we examined the CA125, CA199, CEA and AFP levels in blood and ascites, only to find that the CA125 level alone rose in the tumor-bearing mice. This makes a possibility where CA125 may be used as a biomarker in the model, similar to its clinical application, for prognosis prediction and therapeutic evaluation in future studies.