CD44 variant 6 is involved in the attachment and invasion of endometrial cells to peritoneum

Abstract Objective To study the effects of CD44 standard (CD44s), CD44v3 and CD44v6 overexpression (OE) on immortalized human endometrial epithelial (iEECs) and stroma cells (hESCs) using in vitro assays and a nude mouse xenograft model. As menstrual endometrial cells (MECs) from women with endometriosis have increased adhesion and also express higher levels of CD44 variant 6 (v6), but not v3, compared to MECs from women without endometriosis. Design In vitro studies and In vivo xenograft model Setting Academic Center Patients(S) Deidentified immortalized endometrial epithelial tissue samples a reproductive-aged woman. Interventions OE of CD44s, CD44v3 and CD44v6 was carried out using lipofectamine and their expression verified with mRNA and protein in iEEC and hESCs. The OE cells were used in in vitro studies and in vivo xenograft model compared to plasmid control. Main Outcome Measures The effect of CD44s, CD44v3 and CD44v6 OE on attachment and invasion assays and a xenograft model with immortalized human stromal and epithelial cells. Results Expression of mRNA and protein confirmed appropriate OE of CD44s, CD44v3 and CD44v6 in the different cell types. CD44v6 OE increased attachment of hESCs compared to control (p=0.03). CD44v6 OE did not change attachment of iEECs. There was no difference in attachment in iEECs or hESCs with OE of CD44s or CD44v3. Conclusion Overexpression of CD44v6 increases attachment of ESCs to PMCs in an in vitro assay and in vivo xenograft model. Menstrual endometrial cell type and CD44 variants play a complex role in the development of the early endometriotic lesion.