Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model.

Ovarian cancer is often accompanied by severe ascites. This complication aggravates the disease per se and the chances for its successful treatment. The etiology of ascites is not well understood nor are efficient therapies for ascites available. These empirical observations support the view that ascites might be caused by blocking of lymphatic vessels. Furthermore, it suggests that cancer cells might be the blocking agent and could use lymphatic vessels for metastatic spreading. To test this hypothesis, we used labeled cancer cells in an immuno-competent animal model of ovarian cancer and followed their dissemination. These NuTu-19 cells are ovarian cancer cells derived from normal rat ovarian epithelial cells, the origin of the most frequent ovarian cancer. Thus studying NuTu-19 cell behavior in an animal model is likely to reflect the progression of the human disease. To unambiguously document the migration of NuTu-19 cells from the peritoneum to remote organs, we generated EGFP expressing NuTu-19 cells by transduction with EGFP-lentiviral vectors. The EGFP positive NuTu-19 cells were injected intraperitoneally into immuno-competent FISHER 344 rats, and the metastatic spreading was monitored. Metastases were observed on the peritoneum, the omentum and in the parathymus. This clearly demonstrates that systemic spreading of NuTu-19 ovarian cancer cells is conducted by lymphatic ways. Animals die 7 weeks after injection, with severe ascites, which suggests that blockage of lymphatic drainage by the cancer cell growth is an important complication of the disease.