The Mechanism Whereby PTH Induces Epithelial-mesenchymal Transition And Stemness Of Ovarian Cancer Cells

Ovary is one of the important reproductive organs of female.Ovarian cancer is the leading cause of death from gynecological malignancy and is responsible for 4% of deaths from cancer in women.Parathyroid hormone(PTH),secreted by the chief cell of parathyroid gland,is one of significant peptide hormones which control calcium phosphorous metabolism and bone transformation.In our study,we showed effects of PTH on ovarian cancer's development and investigated the mechanism of PTH's function.In this study,we found that treatment of ovarian cancer cells SKOV3 and ES2 by PTH would induce the epithelial-mesenchymal transition(EMT)process and stemness.PTH promoted cell proliferation,invasion and migration and the formation of spheres and colonies in vitro.Notably,PTH induced the biomarkers expression of EMT and stemness.Results obtained in the present study suggested that PTH induced EMT process and stemness of ovarian cancer cells by a particular mechanism.Moreover,in orthotopic mouse tumor models,the volume and weight of tumor in PTH treatment group were significantly higher than that in control group.we confirmed that PTH also enhanced the EMT and stemness of ovarian cancer cells in vivo.Furthermore,we investigated the mechanism of PTH's function underlying.We found that the effects of PTH on EMT and stemness could be suppressed and abolished when Notch3 signaling was blocked with Notch3 signaling inhibitor GSI-953 or Notch3 siRNA.Taken together,above all findings showed that PTH promoted EMT and stemness of ovarian cancer cells via Notch3 signaling.