Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer

Endometrial cancer
(EC) is the most frequent gynecological cancer.
Tumor dissemination affecting ∼20% of EC patients is characterized
at the primary carcinoma by epithelial-to-mesenchymal transition (EMT)
associated with myometrial infiltration. At distant sites, the interaction
of circulating tumor cells (CTCs) with the microenvironment is crucial
for metastatic colonization, with a participation of the extracellular
vesicles (EVs). We comprehensively approached these primary and secondary
sites to study the impact of tumor EVs on the metastatic efficiency
of CTCs in EC. Tumor EVs in circulation reproduce the epithelial phenotype
predominant in the primary carcinoma, whereas CTCs are characterized
by an EMT phenotype. We modeled this EMT-related clinical scenario
in the Hec1A endometrial cell line and characterized the epithelial-like
EVs in circulation by SILAC proteome analysis. The identification
of proteins involved in cell–cell and cell–matrix interaction
and binding, together with in vitro evidence of an improved adhesion
of CTC to a functionalized endothelium, suggests a contribution of
the epithelial-like EVs in the homing of CTCs at metastatic sites.
Accordingly, adhesion protein LGALS3BP was found to be significantly
enriched in circulating EVs from a cohort of EC patients with a high
risk of recurrence by targeted proteomics (multiple reaction monitoring),
highlighting its potential in liquid biopsy in EC.