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.

Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis

“…In recent years, accumulating evidence has suggested that significant biological differences exist between the eutopic endometria of healthy women and the ectopic endometria of women with endometriosis [3, 23], but few studies have identified significant biochemical differences between the ectopic endometriotic lesions and the putative eutopic precursors [24]. Thus, in our study, we analyzed the differentially expressed peptides between the eutopic and ectopic endometria of OvE patients, a common subtype of endometriosis.…”

‘Omic’ high-throughput technologies in research on pathogenesis of endometriosis: a Review

“…Эндометриоз рассматривается как доброкаче-ственное заболевание, однако он имеет некоторые биологические особенности, характерные для рака, такие как клеточная инвазия, развитие новых крове-носных сосудов, неконтролируемый рост, резистен-ция к апоптозу, способность к метастазированию и хроническое воспаление [51,52]. Исследования по-казали, что эндометриоидные очаги при эндометри-озассоциированном раке яичников проходят много-ступенчатую трансформацию от типичного к ати-пичному эндометриозу, а затем к раку [51].…”

“…Исследования по-казали, что эндометриоидные очаги при эндометри-озассоциированном раке яичников проходят много-ступенчатую трансформацию от типичного к ати-пичному эндометриозу, а затем к раку [51]. Относи-тельно частоты некоторые авторы оценивают риск в 1% для развития опухолей из эндометриальной тка-ни [51][52][53].…”

“…Предполагается, что эпигенети-ческие процессы и соматические генетические изме-нения могут инициировать онкогенез [51][52][53]. J. Gogusev и соавт.…”

The scar constituent Collagen I triggers coordinated collective migration and invasion in a 3D spheroid model of early endometriotic lesions

“…In order to implant, endometrial fragments have to first penetrate either through intact barriers consisting of epithelial cells, basement membranes and collagen or directly through surgical scars and then spread 6 . In this regard, endometriosis shares many similarities with metastatic cancer 7 . Nevertheless, while cancer researchers have devoted considerable attention to dissecting the invasive processes involved in cancer metastases 8 , little is known about invasive processes in endometriosis.…”