Deep quantitative proteomics underlies extensive metabolic reprogramming and cancer-like changes of ectopic endometriotic stromal cells

Endometriosis is a prevalent health condition in women of reproductive age characterized by ectopic growth of endometrial tissue in the extrauterine environment. Thorough understanding of the molecular mechanisms underlying the disease are still lacking and incomplete. We dissect eutopic and ectopic endometrial primary stromal cell proteomes to a depth of nearly 6900 proteins using quantitative mass-spectrometry with a spike-in SILAC standard. Acquired data reveal metabolic reprogramming of ectopic stromal cells of endometriosis with extensive upregulation of glycolysis and down-regulation of oxidative respiration – a wide-spread metabolic phenotype previously described in many cancers. Our results also underlie other molecular changes of ectopic endometriotic stromal cells indicating reduced apoptotic potential, increased cellular adhesiveness/invasiveness and altered immune function. The changes related to metabolism are additionally reflected by attenuated aerobic respiration of ectopic endometrial stromal cells measured by live cell oximetry and by altered mRNA levels. These comprehensive proteomics data refine the current understanding of endometriosis presenting potential new avenues for therapies.