In vitro mesothelial clearance assay that models the early steps of ovarian cancer metastasis
Abstract
Ovarian cancer is the fifth leading cause of cancer related deaths in the United States(1). Despite a positive initial response to therapies, 70 to 90 percent of women with ovarian cancer develop new metastases, and the recurrence is often fatal(2). It is, therefore, necessary to understand how secondary metastases arise in order to develop better treatments for intermediate and late stage ovarian cancer. Ovarian cancer metastasis occurs when malignant cells detach from the primary tumor site and disseminate throughout the peritoneal cavity. The disseminated cells can form multicellular clusters, or spheroids, that will either remain unattached, or implant onto organs within the peritoneal cavity(3) (Figure 1, Movie 1). All of the organs within the peritoneal cavity are lined with a single, continuous, layer of mesothelial cells(4-6) (Figure 2). However, mesothelial cells are absent from underneath peritoneal tumor masses, as revealed by electron micrograph studies of excised human tumor tissue sections(3,5-7) (Figure 2). This suggests that mesothelial cells are excluded from underneath the tumor mass by an unknown process. Previous in vitro experiments demonstrated that primary ovarian cancer cells attach more efficiently to extracellular matrix than to mesothelial cells(8), and more recent studies showed that primary peritoneal mesothelial cells actually provide a barrier to ovarian cancer cell adhesion and invasion (as compared to adhesion and invasion on substrates that…
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