title: Deep Quantitative Proteomics Reveals Extensive Metabolic Reprogramming and Cancer-Like Changes of Ectopic Endometriotic Stromal Cells.
abstract: Endometriosis is a prevalent health condition in women of reproductive age characterized by ectopic growth of endometrial-like tissue in the extrauterine environment. Thorough understanding of the molecular mechanisms underlying the disease is still incomplete. We dissected 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 revealed metabolic reprogramming of ectopic stromal cells with extensive upregulation of glycolysis and downregulation of oxidative respiration, a widespread metabolic phenotype known as the Warburg effect and previously described in many cancers. These changes in metabolism are additionally accompanied by attenuated aerobic respiration of ectopic endometrial stromal cells as measured by live-cell oximetry and by altered mRNA levels of respective enzyme complexes. Our results additionally highlight other molecular changes of ectopic endometriotic stromal cells indicating reduced apoptotic potential, increased cellular invasiveness and adhesiveness, and altered immune function. Altogether, these comprehensive proteomics data refine the current understanding of endometriosis pathogenesis and present new avenues for therapies.
authors.affiliation: Proteomics Core Facility, Institute of Technology, University of Tartu , Nooruse 1, Tartu, Estonia.|Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.|Tartu University Women's Clinic , L. Puusepa 8, Tartu, Estonia.
authors.forename: Sergo
authors.initials: S
authors.lastname: Kasvandik
authors.affiliation: Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.
authors.forename: Külli
authors.initials: K
authors.lastname: Samuel
authors.affiliation: Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.|Tartu University Women's Clinic , L. Puusepa 8, Tartu, Estonia.
authors.forename: Maire
authors.initials: M
authors.lastname: Peters
authors.affiliation: Chair of Pathological Physiology, Institute of Bio- and Translational Medicine, University of Tartu , Ravila 19, Tartu, Estonia.
authors.forename: Margus
authors.initials: M
authors.lastname: Eimre
authors.affiliation: Chair of Pathological Physiology, Institute of Bio- and Translational Medicine, University of Tartu , Ravila 19, Tartu, Estonia.
authors.forename: Nadežda
authors.initials: N
authors.lastname: Peet
authors.affiliation: Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.|Tartu University Women's Clinic , L. Puusepa 8, Tartu, Estonia.
authors.forename: Anne Mari
authors.initials: AM
authors.lastname: Roost
authors.affiliation: Tartu University Hospital, Women's Clinic , L. Puusepa 8, Tartu, Estonia.
authors.forename: Lee
authors.initials: L
authors.lastname: Padrik
authors.affiliation: Chair of Pathological Physiology, Institute of Bio- and Translational Medicine, University of Tartu , Ravila 19, Tartu, Estonia.
authors.forename: Kalju
authors.initials: K
authors.lastname: Paju
authors.affiliation: Proteomics Core Facility, Institute of Technology, University of Tartu , Nooruse 1, Tartu, Estonia.
authors.forename: Lauri
authors.initials: L
authors.lastname: Peil
authors.affiliation: Competence Centre on Health Technologies , Tiigi 61b, Tartu, Estonia.|Tartu University Women's Clinic , L. Puusepa 8, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
mesh_terms: D002478:Cells, Cultured; D002853:Chromatography, Liquid; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010092:Oximetry; D010101:Oxygen Consumption / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome
keywords: SILAC; Warburg effect; endometrial stromal cells; endometriosis; endometrium; metabolism; peritoneal endometriosis; quantitative proteomics