Loss of retinal cadherin facilitates mammary tumor progression and metastasis

Georgia Agiostratidou, Maomi Li, Kimita Suyama, Ines Badano, Rinat Keren, Su Chung, Amy Anzovino, James Hulit, Binzhi Qian, Boumediene Bouzahzah, Eliseo Eugenin, Olivier Loudig, Greg R. Phillips, Joseph Locker, Rachel B. Hazan

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5030-5038
Number of pages9
JournalCancer Research
Volume69
Issue number12
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Agiostratidou, G., Li, M., Suyama, K., Badano, I., Keren, R., Chung, S., Anzovino, A., Hulit, J., Qian, B., Bouzahzah, B., Eugenin, E., Loudig, O., Phillips, G. R., Locker, J., & Hazan, R. B. (2009). Loss of retinal cadherin facilitates mammary tumor progression and metastasis. Cancer Research, 69(12), 5030-5038. https://doi.org/10.1158/0008-5472.CAN-08-4007