Impaired expression of ecto-nucleotidases in human endometrial pathologies

Abstract

The levels of extracellular ATP and its derivatives such as adenosine are impaired in the tissue microenvironment during tissue stress conditions such as hypoxia, infection, metabolic stress, tumor transformation and inflammation. Ecto-nucleotidases are the main regulators of extracellular ATP and adenosine levels. The aim of the present work is to upgrade our understanding of the role and location of ecto-nucleotidases in the context of two endometrial pathologies: cancer and endometriosis, as well as to investigate new diagnostic and treatment modalities based on the inhibition of ecto-nucleotidases' activities. We have analyzed by means of immunolabeling and in situ enzyme histochemistry human endometrial samples from: 1) endometrial tumors, and, 2) eutopic endometria as well as ectòpic endometriotic lesions from women with endometriosis. We have also studied endometrial cell cultures to evaluate the consequences of the overexpression of ecto-nucleotidases in their proliferative and invasive phenotypes. Ecto-nucleotidases showed impaired expression in pathological conditions when compared with non-pathological endometria. This altered pattern includes changes in expression levels and changes in protein localization, mainly a switch between epithelium and stroma. Overexpression of ecto-nucleotidases in endometrial cell cultures lead to changes in the proliferation and invasion rates. Impaired ecto-nucleotidases activities in endometrium might contribute to the pathogenesis and maintenance of endometrial pathologies with an inflammatory component such as cancer and endometriosis.