Deep Quantitative Proteomics Reveals 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-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.