Objective High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian tumors, and is the 5th leading cause of cancer related deaths among women in the western world. Recent studies have pointed at the fimbriae of the fallopian tube (FT) as one of HGSOC’s main origins. The existence of FT stem cells (SCs) has been suggested, however, their isolation and characterization have been so far elusive. Given the potential of SCs to accumulate mutations, these cells may represent one of the cellular origins of HGSOC.This project is aimed at identifying SCs of the FT, evaluating their tumorigenic capacity and establishing a novel in-vitro human model for HGSOC development. Preliminary screening experiments of well-established SC markers have identified Lgr6 and Troy expression in the mouse oviduct. These putative SC populations will be further characterized and their capacity to maintain tissue homeostasis will be analyzed by lineage tracing experiments. Next, mouse and human organoid culture systems of FT and HGSOC will be generated. Mutating normal FT organoids in specific genes, using the CRISPR/Cas9 system, will enable following putative SCs tumorigenic capacity upon their injection to mice. Furthermore, it will generate an innovative in-vitro model of ovarian cancer development. Finally, HGSOC organoids will be used to model and follow chemotherapy resistance acquisition. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesclinical medicineallergologydrug allergymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinetransplantation Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW Net EU contribution € 177 598,80 Address KLOVENIERSBURGWAL 29 HET TRIPPENHUIS 1011 JV AMSTERDAM Netherlands See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 177 598,80
