Expression pattern of integrin adhesion molecules in endometriosis and human endometrium

Abstract

Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins alphav, alpha2beta1, alpha3beta1, alpha3, alpha6, beta1, beta2 and beta3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin alpha6 was expressed in all endometriotic and endometrium samples. The integrin alpha3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin beta3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferentiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum.

Altered expression of claudin-3 and claudin-4 in ectopic endometrium of women with endometriosis

“…In the present study we found that expression of claudin-3 and claudin-4 in eutopic endometrium from women with endometriosis was lower compared with normal endometrium from women without endometriosis, but the difference was not statistically significant. This result agrees with that from a previous study, in which no difference was found in integrin expression between endometrium from women with and without endometriosis (21). In contrast, some evidence has suggested that the eutopic endometrium from women with endometriosis has altered expression of several components of the junctional complexes, such as connexin, cadherin, and catenin (22,23).…”

Novel estrogen-related genes and potential biomarkers of ovarian endometriosis identified by differential expression analysis

“…Additionally, cancercell migration promoting collagen triple helix repeat containing 1 (CTHRC1) [37] and Rho GTPase activating protein (ARHGAP) family genes, which are implicated in actin remodeling, cell polarity and migration [38], were up-regulated in the endometriosis group. We also observed a 3-fold down-regulation of integrin alpha 1 subunit (ITGA2), which changes cell-cell and cell-matrix interactions that are important for the development of endometriosis [39]. We thus found aberrant mRNA levels of several novel genes associated with cell migration and cell adhesion: ADAM23, ITGB5, FNDC1, CTHRC1 and ARHGAP25.…”

Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis

“…The a V b 3 integrins transmit signals to the cytoskeletal structures of cells and usually mediate expression of fibronectin and vibronectin (31) and have been localized in endometriotic lesions and endometrium in women with and without endometriosis during both follicular or secretory phases (32). Therefore, we hypothesise that a V b 3 integrin may facilitate the adhesion of endometrial cells, especially during menstruation to the pelvic peritoneum, and lead to the development of endometriosis.…”