Maria Sol Recouvreux, PhD
About Project
The Role of Ciliated Cells in Preventing Fallopian Tube Cancer Initiation
PROJECT SUMMARY
Ovarian cancer is the most fatal gynecologic cancer. While curative treatments exist for early-stage cancers, there is a lack of specific biomarkers for detecting preneoplastic lesions, which usually occur in the fallopian tube epithelia (FTE). Normal FTE consists of small clusters of secretory and ciliated cells intermixed in an approximately 1:1 ratio. It is believed that hormones and growth factors in the follicular fluid expose FTE to genotoxic stress during ovulation and that escape from the stress-induced cell death leads to an aberrant accumulation of damaged secretory cells, which is associated with an increased risk of ovarian cancer and is more common in women with germline BRCA1 mutations. However, the morphologic changes and molecular mechanisms that lead to secretory cell transformation are unknown. Specifically, the role of ciliated cells in the formation of precursor FTE lesions is unknown. We found that BRCA1 mutation carriers have a higher ratio of secretory to ciliated cells than non-carriers. We propose that loss of ciliated cells creates a favorable microenvironment for secretory cell transformation in BRCA1 mutant FTE providing that other conditions, such as hormonal changes and genotoxic stress, coincide and tip the balance toward uncontrolled proliferation. We will use human and mouse FTE organoids to test the hypothesis that ciliated cells protect secretory cells from genotoxic stress. Better understanding of the interplay between predisposing genetic mutations and the microenvironmental changes that precede ovarian cancer initiation will assist in the development of new strategies for ovarian cancer prevention and detection.
