TARGETING THE WNT PATHWAY IN OVARIAN CANCER DISSEMINATION

Abstract

EPITHELIAL OVARIAN CANCER (EOC) IS THE MOST PREVALENT FORM OF OVARIAN CANCER, WITH ITS? ASYMPTOMATIC NATURE MAKING EARLY DETECTION DIFFICULT, RESULTING IN LATE-STAGE DIAGNOSIS WITH POOR PROGNOSTIC OUTCOME. EOC CELLS METASTASIZE BY FORMING SPHEROIDS THAT DISSOCIATE FROM THE PRIMARY TUMOUR, RESUSPENDING IN THE PATIENT ASCITES, EVENTUALLY REATTACHING ALONG THE PERITONEAL CAVITY. PREVIOUSLY, IN VITRO CULTURE OF OVARIAN CANCER SPHEROIDS SHOWED UP-REGULATED EXPRESSION OF THE WNT RECEPTOR FRIZZLED-7 (FZD7). FURTHERMORE, FZD7 EXPRESSION WAS ENRICHED IN EOC CELL LINES DISPLAYING A STEM-LIKE MOLECULAR EXPRESSION PROFILE, SUGGESTING A ROLE OF FZD7 IN THE MAINTENANCE OF SPHEROIDS IN OVARIAN CANCER. IN THIS STUDY, RNAI OF FZD7 IN SPHEROID-FORMING EOC CELLS DISRUPTED SPHEROID FORMATION BY INDUCING ANOIKIS IN SUSPENSION CULTURES, FURTHER SUBSTANTIATED BY INCREASED ANNEXIN-V POPULATION AND THE UP-REGULATION OF APOPTOTIC MARKERS. THE FINDINGS OF THIS STUDY SUGGEST WNT SIGNALLING PROTECT EOC CELLS FROM