Artículos de revistas
Loss of retinal cadherin facilitates mammary tumor progression and metastasis
Fecha
2009-06Registro en:
Agiostratidou, Georgia; Li, Maomi; Suyama, Kimita; Badano, Ines; Keren, Rinat; et al.; Loss of retinal cadherin facilitates mammary tumor progression and metastasis; American Association for Cancer Research; Cancer Research; 69; 12; 6-2009; 5030-5038
0008-5472
CONICET Digital
CONICET
Autor
Agiostratidou, Georgia
Li, Maomi
Suyama, Kimita
Badano, Ines
Keren, Rinat
Chung, Su
Anzovino, Amy
Hulit, James
Qian, Binzhi
Bouzahzah, Boumediene
Eugenin, Eliseo
Loudig, Olivier
Phillips, Greg R.
Locker, Joseph
Hazan, Rachel B.
Resumen
The mammary epithelium is thought to be stabilized by cellcell adhesion mediated mainly by E-cadherin (E-cad). Here, we show that another cadherin, retinal cadherin (R-cad), is critical for maintenance of the epithelial phenotype. R-cad is expressed in nontransformed mammary epithelium but absent from tumorigenic cell lines. In vivo, R-cad was prominently expressed in the epithelium of both ducts and lobules. In human breast cancer, R-cad was down-regulated with tumor progression, with high expression in ductal carcinoma in situ and reduced expression in invasive duct carcinomas. By comparison, E-cad expression persisted in invasive breast tumors and cell lines where R-cad was lost. Consistent with these findings, R-cad knockdown in normal mammary epithelium stimulated invasiveness and disrupted formation of acini despite continued E-cad expression. Conversely, R-cad overexpression in aggressive cell lines induced glandular morphogenesis and inhibited invasiveness, tumor formation, and lung colonization. R-cad also suppressed the matrix metalloproteinase 1 (MMP1), MMP2, and cyclooxygenase 2 gene expression associated with pulmonary metastasis. The data suggest that R-cad is an adhesion molecule of the mammary epithelium, which acts as a critical regulator of the normal phenotype. As a result, R-cad loss contributes to epithelial suppression and metastatic progression. ©2009 American Association for Cancer Research.