A clinically relevant orthotopic implantation nude mouse model of human epithelial ovarian cancer--based on consecutive observation

The aim of this study is to establish an orthotopic implantation nude mouse model of epithelial ovarian cancer (EOC) and observe its biologic features. A human ovarian tumor line SKOV3ipl previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 64 nude mice. Every week eight mice were taken randomly, and the tumor growth pattern and extent of metastatic disease were monitored continuously. Those mice that died of disease were necropsied and the end date was recorded. The orthotopic implanted tumors demonstrated a 100% take rate. Three weeks after implantation the tumors grew fast and weighed 1149 +/- 152 mg, and 5 weeks after implantation the tumors reached a flat stage. The tumors metastasized more often to peritoneum (32/56) and diaphragm (18/56), then to pelvic lymph nodes (11/56) and lung (10/56), and then to the seldom invaded organs including the pancreas, the liver, the contralateral ovary, and the para-aortic lymph node. Eight nude mice became exhausted 7 weeks after implantation and died within 68 days after implantation. Our study, utilizing the SKOV3ipl cell, is the first model of consecutive observation of the process of invasion and metastasis of EOC. It should be useful in understanding the molecular biology of EOC and in the development of therapeutic modalities against metastasis.