TY - JOUR
T1 - Loss of retinal cadherin facilitates mammary tumor progression and metastasis
AU - Agiostratidou, Georgia
AU - Li, Maomi
AU - Suyama, Kimita
AU - Badano, Ines
AU - Keren, Rinat
AU - Chung, Su
AU - Anzovino, Amy
AU - Hulit, James
AU - Qian, Binzhi
AU - Bouzahzah, Boumediene
AU - Eugenin, Eliseo
AU - Loudig, Olivier
AU - Phillips, Greg R.
AU - Locker, Joseph
AU - Hazan, Rachel B.
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-08-4007
DO - 10.1158/0008-5472.CAN-08-4007
M3 - Article
C2 - 19491271
AN - SCOPUS:67449164597
SN - 0008-5472
VL - 69
SP - 5030
EP - 5038
JO - Cancer Research
JF - Cancer Research
IS - 12
ER -