Deep Quantitative\nProteomics Reveals Extensive Metabolic\nReprogramming and Cancer-Like Changes of Ectopic Endometriotic Stromal\nCells

Endometriosis\nis a prevalent health condition in women of reproductive\nage characterized by ectopic growth of endometrial-like tissue in\nthe extrauterine environment. Thorough understanding of the molecular\nmechanisms underlying the disease is still incomplete. We dissected\neutopic and ectopic endometrial primary stromal cell proteomes to\na depth of nearly 6900 proteins using quantitative mass spectrometry\nwith a spike-in SILAC standard. Acquired data revealed metabolic reprogramming\nof ectopic stromal cells with extensive upregulation of glycolysis\nand downregulation of oxidative respiration, a widespread metabolic\nphenotype known as the Warburg effect and previously described in\nmany cancers. These changes in metabolism are additionally accompanied\nby attenuated aerobic respiration of ectopic endometrial stromal cells\nas measured by live-cell oximetry and by altered mRNA levels of respective\nenzyme complexes. Our results additionally highlight other molecular\nchanges of ectopic endometriotic stromal cells indicating reduced\napoptotic potential, increased cellular invasiveness and adhesiveness,\nand altered immune function. Altogether, these comprehensive proteomics\ndata refine the current understanding of endometriosis pathogenesis\nand present new avenues for therapies.