Intraperitoneale Metastasierung des Ovarialkarzinoms: Funktionelle Analyse der Tumor-Mesothel-Interaktion in einem neu etablierten dreidimensionalen Invasionsassay

Ovarian cancer, which affects more than 7000 women in Germany every year, has an average 5-year-survival rate of only 40% and is thus one of the most lethal cancers among females. The lack of successful screening parameters plus the fact that women initially do not suffer from symptoms lead to a late initial diagnosis with advanced stages in 75% of patients. Currently, physicians still lack a proper diagnostic approach to detect peritoneal metastasis and targeted therapies are still desperately needed. This novel three-dimensional invasion-assay on primary ovarian cancer cells enables a better in-vitro model for future analysis of peritoneal metastasis. To reproduce the three-dimensional structure of the peritoneal wall human primary mesothelial cells were cultured on polycarbonate Transwells until they reached confluency. Primary ovarian cancer cells isolated from malignant ascites of women suffering from high-grade serous ovarian cancer were placed above this mesothelial monolayer to further analyze their invasion. Thereby, we were able to identify mesothelial cells as significant promoters of ovarian cancer cell invasion. After incubation with conditioned medium of human mesothelial cells more cancer cell invasion was seen, which points to a possible enhancing role of soluble factors in the invasion process. Those effects could be reproduced in different patients and in a concentration dependent manner. Relevant effects of Lysophosphatidic acids could be excluded performing invasion- assays with lysophosphatidic acids only. This novel invasion-assay thus holds great potential to further investigate key processes of peritoneal metastasis in ovarian cancer. The identification of soluble factors secreted by mesothelial cells as a promotor of ovarian cancer invasion might provide a possible target for therapeutic approaches in patients suffering from ovarian cancer in the future.