Endometrial cancer (EC) is the most frequent gynecological cancer and the second cause of death from gynecological cancer in Switzerland. The purpose of this project is to investigate the biological mechanisms driving EC progression and invasion at early stage with a focus on post-biosynthetic modifications of anticoagulant heparan sulfate (aHS) proteoglycans. We show a decreased expression of aHS that correlates with tumor invasiveness. Gene expression profiling reveals an upregulation of aHS catabolic enzyme heparanase in the tumor micro environment inducing enzymatic remodeling of extracellular matrix and activation of HS-related oncogenic pathways such as grow factors signaling. We next aimed to target in vitro HS-degrading activity of heparanase to restore normal biological activities of tumor cells. In vitro inhibition of tumorigenesis-related processes under HS derivatives supports the prognostic and therapeutical potential of aHS as modulator of tumor cell invasion in the endometrium.