The Depolarized Expression of the Alpha-6 Integrin Subunit in the Endometria of Women With Endometriosis

Abstract

Objective: The current study sought to compare the endometrial localization of the integrin subunit alpha-6 in women with endometriosis and women without the disease. Alpha-6 integrins have an important function, not only in the attachment of cells to the extracellular matrix and laminin, but they also serve as inductors of cell migration and invasion, depending on their pattern of expression in the cell membrane.

Methods: The endometriosis group consisted of 32 women with a confirmed diagnosis of endometriosis by laparoscopy or laparotomy. The control group consisted of 20 women not having endometriosis or any other gynecologic disease at laparoscopy. Endometria were obtained by biopsy. Immunohistochemical techniques were used to assess alpha-6- localization. In each section, the percentage of positive cells and the localization of expression were evaluated.

Results: All glandular cells expressed alpha-6- in all of the samples but presented two different patterns, either only in the basal side of the cells (polarized) or also in other sides of the cell (depolarized). The percentage of samples showing depolarized expression was significantly higher in the endometriosis group (66.6% vs 15.8%, χ² = 12.09, P = .001).

Conclusions: The endometria of women with endometriosis more frequently show a depolarized expression of integrin subunit alpha-6, a characteristic usually found in highly proliferating cells with migrating and invasive abilities.

Keywords

Endometriosis integrin alpha-6 endometrium depolarization

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References

1. Sampson J . Metastatic or embolic endometriosis due to menstrual dissemination of endometrial tissue into venous circulation. Am J Pathol 1927;3:93-110.

2. Sharpe-Timms K . Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci 2001;943:131-147.

3. Lessey BA , Castelbaum AJ , Sawin SW , et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab 1994;79:643-649.

4. Falcioni R , Antonini A , Nistico P , et al. Alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines. Exp Cell Res 1997;236:76-85.

5. Lussier C , Basora N , Bouatrouss Y , Beaulieu JF . Integrins as mediators of epithelial cell-matrix interactions in the human small intestinal mucosa. Microsc Res Tech 2000;51:169-178.

6. Mercurio AM , Rabinovitz I , Shaw LM . The alpha 6 beta 4 integrin and epithelial cell migration. Curr Opin Cell Biol 2001;13:541-545.

7. Mercurio AM , Bachelder RE , Chung J , et al. Integrin laminin receptors and breast carcinoma progression. J Mammary Gland Biol Neoplasia 2001;6:299-309.

8. Chung J , Bachelder RE , Lipscomb EA , Shaw LM , Mercurio AM . Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: A survival mechanism for carcinoma cells. J Cell Biol 2002;158:165-174.

9. Giannelli G , Astigiano S , Antonaci S , et al. Role of the alpha3beta1 and alpha6beta4 integrins in tumor invasion. Clin Exp Metastasis 2002;19:217-223.

10.

10. Sashiyama H , Shino Y , Sakao S , et al. Alteration of integrin expression relates to malignant progression of human papillomavirus-immortalized esophageal keratinocytes. Cancer Lett 2002;177:21-28.

11.

11. Lessey BA , Damjanovich L , Coutifaris C , Castelbaum A , Albelda SM , Buck CA . Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest 1992;90:188-195.

12.

12. Tabibzadeh S . Patterns of expression of integrin molecules in human endometrium throughout the menstrual cycle. Hum Reprod 1992;7:876-882.

13.

13. Bridges JE , Prentice A , Roche W , Englefield P , Thomas EJ . Expression of integrin adhesion molecules in endometrium and endometriosis. Br J Obstet Gynaecol 1994;101:696-700.

14.

14. Lanteri E , Pistritto M , Bartoloni G , Cordaro S , Stivala F , Montoneri C . Expression of alpha6 and beta4 integrin subunits on human endometrium throughout the menstrual cycle and during early pregnancy. Fertil Steril 1998;69:37-40.

15.

15. Murray MJ , Zhang J , Lessey BA . Expression of alpha6 and beta4 integrin subunits throughout the menstrual cycle: no correlation with uterine receptivity. Fertil Steril 1999;72:522-526.

16.

16. Koks CA , Groothuis PG , Dunselman GA , de Goeuij AF , Evers JL . Adhesion of menstrual endometrium to extracellular matrix: The possible role of integrin alpha(6)beta(1) and laminin interaction. Mol Hum Reprod 2000;6:170-177.

17.

17. Park KR , Inoue T , Ueda M , et al. CD9 is expressed on human endometrial epithelial cells in association with integrins alpha(6), alpha(3) and beta(1). Mol Hum Reprod 2000;6:252-257.

18.

18. Regidor PA , Vogel C , Regidor M , Schindler AE , Winterhager E . Expression pattern of integrin adhesion molecules in endometriosis and human endometrium. Hum Reprod Update 1998;4:710-718.

19.

19. Hogg N , Bates PA . Genetic analysis of integrin function in man: LAD-1 and other syndromes. Matrix Biol 2000;19:211-222.

20.

20. De Luca M , Pellegrini G , Zambruno G , Marchisio PC . Role of integrins in cell adhesion and polarity in normal keratinocytes and human skin pathologies. J Dermatol 1994;21:821-828.

21.

21. Zeitvogel A , Baumann R , Starzinski-Powitz A . Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am J Pathol 2001;159:1839-1852.

22.

22. van der Linden PJ , de Goeij AF , Dunselmna GA , Erkens HW , Evers JL . Expression of cadherins and integrins in human endometrium throughout the menstrual cycle. Fertil Steril 1995;63:1210-1216.