RRC ID 70168
Author Yamashita S, Hashimoto K, Sawada I, Ogawa M, Nakatsuka E, Kawano M, Kinose Y, Kodama M, Sawada K, Kimura T.
Title Endometrial galectin-3 causes endometriosis by supporting eutopic endometrial cell survival and engraftment in the peritoneal cavity.
Journal Am J Reprod Immunol
Abstract PROBLEM:The pathogenesis of endometriosis remains unclear. Endometrial cells in retrograde menstruation are considered the source of endometriosis; therefore, we hypothesized that the eutopic endometrium may provide clues regarding the pathogenesis. We aimed to clarify the role of eutopic endometrial cells in endometriosis development.
METHOD OF STUDY:Eutopic endometrial tissues were obtained from patients with or without endometriosis, and expression of cell surface molecules in eutopic endometrial stromal cells (ESCs) was evaluated via iTRAQ-based proteomic analysis. Based on the results, we focused on galectin-3. Galectin-3 expression in clinical samples was confirmed by immunohistochemistry and western blot analysis. The concentration of secreted galectin-3 was measured using enzyme-linked immunosorbent assays. Adhesion and migration of ESCs were evaluated by in-vitro adhesion and wound healing assays. The cytotoxicity of natural killer cells was measured via calcein release assays. Cell proliferation was measured using the CyQUANT Cell Proliferation Assay Kit.
RESULTS:iTRAQ analysis revealed that galectin-3 expression was specifically elevated in the ESCs from endometriosis patients. Immunohistochemistry confirmed galectin-3 overexpression in the eutopic endometrium of endometriosis, irrespective of the menstrual phase. Galectin-3 was overexpressed and secreted by the eutopic ESCs from patients with endometriosis compared to that from patients without endometriosis. Galectin-3 expression in ESCs increased adhesion and migration, whereas galectin-3 inhibitors impaired these processes. Galectin-3 reduced the cytotoxicity of natural killer cells toward ESCs, while not affecting cell proliferation.
CONCLUSION:Galectin-3 promotes peritoneal engraftment of ESCs due to impaired immune surveillance in the peritoneal cavity and increases ESCs adhesion and migration to the peritoneum.
Volume 87(6)
Pages e13533
Published 2022-6-1
DOI 10.1111/aji.13533
PMID 35366371
MeSH Antigens, Neoplasm Biomarkers, Tumor Cell Survival Endometriosis* Endometrium / pathology Female Galectin 3 / genetics Galectin 3 / metabolism Humans Peritoneal Cavity / pathology Proteomics Stromal Cells / metabolism
IF 2.739
Human and Animal Cells 293gp(RCB2354)