Investigating the Role of Metabolite Signaling in Primary Metastasis of High Grade Serous Ovarian Cancer

High grade serous ovarian cancer (HGSOC) is the most lethal and most common histotype of ovarian cancer. Unfortunately, many patients present in late stages of disease due to a lack of screening modalities. This lack of early monitoring is partly due to a deficit of understanding in the field about the early pathologic processes in HGSOC. Recently the field has come to understand that HGSOC can originate in fallopian tube epithelium, but how transformed cells migrate to and colonize the ovary is yet unknown. Hence, the bulk of this dissertation is focused on identifying signals that are involved in the primary metastasis of tumorigenic fallopian tube epithelial cells to the ovary. We utilized imaging mass spectrometry to identify that tumorigenic fallopian tube epithelial cells and human ovarian cancer cells secrete a protein called SPARC which enables the ovary to release norepinephrine. We have also determined that norepinephrine can increase invasion in tumorigenic fallopian tube epithelial cells and increase epithelial to mesenchymal transition hallmark proteins in human ovarian cancer cells. Further, we have identified that different mutations in fallopian tube epithelial cells cause the ovary to release distinct sets of metabolites as measured by LC-MS/MS. Additionally, we have identified that kaempferol, a flavonoid found in nature, has partial progestogenic activity in mice and may represent a potential non-synthetic treatment for symptoms for which progesterone is a common treatment. Ultimately, this body of work attempts to understand and address the current lack of clarity surrounding primary metastasis in HGSOC in hopes of identifying future avenues of prevention or treatment.