Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants

Abstract

Objective-We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants' potential role in this process. Design-In vitro study. Setting-Academic medical Center Patient(s)-Fertility patients with and without endometriosisIntervention(s)-Menstrual endometrium was collected from women with and without endometriosis confirmed surgically. The adherence of ESC/EECs to PMCs was measured. ESC/EEC CD44 splice variants were assessed using dot blot analysis. Results-ESCs and EECs from women with endometriosis demonstrated increased adherence toPMCs. The predominant CD44 splice variants expressed by ESCs and EECs from women with and without endometriosis were v3, v6, v7, v8, v9, and v10. ESCs and EECs from women with endometriosis were more likely to express v6, v7, v8 or v9.Conclusions-Increased eutopic endometrial-PMC adherence and CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions. Elucidation of factors controlling this expression may lead to novel endometriosis therapies.

New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal

“…The endometriotic cells were more likely to express the CD44 splice variants v6, v7, v8 and v9 [63]. Increased CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions [63].…”

“…TGFb increased expression of enzymes synthesising hyaluronan [62]. Adherence of endometrial cells to peritoneal mesothelial cells is also regulated by CD44 interactions with hyaluronan [60,63]. The endometriotic cells were more likely to express the CD44 splice variants v6, v7, v8 and v9 [63].…”

“…Adherence of endometrial cells to peritoneal mesothelial cells is also regulated by CD44 interactions with hyaluronan [60,63]. The endometriotic cells were more likely to express the CD44 splice variants v6, v7, v8 and v9 [63]. Increased CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions [63].…”

Simvastatin Decreases Invasiveness of Human Endometrial Stromal Cells1

“…CD44 is a transmembrane protein adhesion molecule that plays a role in the attachment of endometrial cells to the peritoneum [3] and may be crucial for the initiation of endometriosis [4]. As presented by Griffith et al [5], menstrual endometrial stromal cells derived from women with endometriosis exhibit an increased rate of adherence to peritoneal mesothelium and elevated expression of several isoforms of CD44. Elevated levels of soluble forms of CD44 were also detected in the peritoneal fluid of patients with endometriosis [6].…”

Importance of genital endometriosis in pathogenesis of infertility

“…Эти процессы находятся под контролем эстрадиола, который увеличивает миграционную способность клеток эндометрия [32]. Показано, что клетки эндометрия больных эндометриозом обладают повышенными адге-зивными свойствами, что является одним из зве-ньев патогенеза заболевания [38].…”