Epithelial ovarian cancer (EOC) is the 5th leading cause of cancer death in women. Although numerous studies have investigated the molecular drivers of EOC dissemination, effective strategies to limit EOC spread are lacking. Ideally, a regulatory molecule that acts on multiple signaling pathways associated with tumor maintenance and progression will be the optimal target for the development of therapeutics. To this end, coagulation factor XII (FXII) and its receptor urokinase plasminogen activator receptor (uPAR) represent optimal therapeutic targets because uPAR is overexpressed in more than 90% of EOC tumors and FXII has been shown to be upregulated in the peritoneum of EOC patients and promotes dissemination. We recently identified novel FXII functions mediated through uPAR that lead to neutrophil activation. Neutrophils are increasingly recognized to be important players in the tumor microenvironment (TME) that promote EOC tumor growth and spread. Our preliminary data strongly suggest co-operative mechanistic roles for FXII and uPAR in neutrophils and EOC cells that contribute to tumor progression. Presently, we aim to establish the differential contributions of host and tumor FXII in EOC biology and examine the effects of FXII-induced neutrophil activation on the TME. Lastly, in collaborative work, we aim to investigate the therapeutic potential of FXII inhibitors on EOC progression.