Cell surfactomes of two endometrial epithelial cell lines that differ in their adhesiveness to embryonic cells

Abstract

Adhesiveness of the endometrial epithelium to an embryo plays a critical role in the initiation of pregnancy. Loss or gain of adhesiveness also dictates the potential of endometrial epithelial cells to metastasize, an event that can result from certain genetic insults. A proteomics-based exploration of the "adhesiveness" these epithelial cells was employed that could identify targets that could disrupt embryo-endometrium interactions and/or metastasis of endometrial cancer cells. The present study defined the surfactomes of two human endometrial epithelial cell lines known for their differential adhesiveness to embryonic cells. Comparative, two-dimensional electrophoretic analysis of the surfactomes of RL95-2 (exhibiting higher adhesiveness to the embryonic cell line JAr) and HEC-1A (exhibiting reduced adhesiveness to JAr cells) revealed 55 differentially enriched proteins. Of these, 10 proteins were identified by MALDI-TOF/TOF or LC-MS/MS. TUBB2C, ADAMTS3, and elongation factor beta were more abundant on the HEC-1A cell surface whereas HSP27, HSPA9, GP96, CRT, Tapasin-ERP57, PDI, and β-actin were more abundant on the RL95-2 cell surface. Nano LC-MS/MS was also employed to generate a more comprehensive surfactomes of RL95-2 and HEC-1A. The study also demonstrated a pro-adhesive role of CRT and HSPA9 and an anti-adhesive role of TUBB2C populations found on the cell surface. In brief, this study identifies the cell-surface protein complements of two human endometrial epithelial cell lines, and reveals the role of three proteins in heterotypic cell adhesion.

Secretory Proteomic Responses of Endometrial Epithelial Cells to Trophoblast-Derived Extracellular Vesicles

“…The in vitro model we used consisted of JAr and RL95-2 cells and is a well-established cell culture model that has been frequently used in our laboratory for many other studies to simulate embryo-endometrial interactions [12,13,93,94]. However, there is a need in the field for more advanced models to simulate the embryo-maternal interface during the Major protein changes were associated with glutathione metabolism, cellular responses to oxidative stress, cellular redox homeostasis, gluconeogenesis, tight junctions, and protein processing in the endoplasmic reticulum (ER).…”

ADAMTS‐3, ‐13, ‐16, and ‐19 levels in patients with habitual abortion

“…It has been reported that ADAMTS proteinases play roles in follicle development, ovulation, and corpus luteum formation [15,20,21]. ADAMTS‐3 is important in cell adhesion in endometrial cell lines, and it has been shown that ADAMTS‐3 expression was abundant on the surface of a group of endometrial cell lines, showing reduced adhesiveness to JAr cells [22]. In addition, a recent experimental study showed that ADAMTS‐3 is able to activate vascular endothelial growth factor by proteolytic cleavage; however, the mechanism is poorly explained [23].…”

Using organoids to investigate human endometrial receptivity

“…Another dysregulated protein is Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9). HSPA9 is localized to the endometrial epithelial cell surface and functionally it facilitates endometrial epithelial cell adhesiveness to trophoblast cells (27). Further investigations of these organoid apical secreted proteins will likely uncover new biomarkers and treatment targets for endometrial receptivity that are epithelial cell specific.…”