Abstract 3357: Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases

Abstract

Abstract Epithelial to mesenchymal transition (EMT) is an oft-studied mechanism for the initiation of metastasis. We have recently shown that once cancer cells disseminate to a secondary organ, a mesenchymal to epithelial reverting transition (MErT) can occur, which we postulate is to enable metastatic colonization. Despite a wealth of in vitro and in vivo studies, evidence of MErT in human specimens is rare and difficult to document because clinically detectable metastases are typically past the micrometastatic stage at which this transition is most likely evident. We obtained specimens of primary and metastatic tumors from breast and prostate cancer patients and evaluated expression of various epithelial and mesenchymal markers by immunohistochemistry. Breast cancer metastases exhibited increased expression of membranous E-cadherin and β-catenin compared to primary tumors, consistent with EMT at the primary site and MErT at the metastatic site. Expression of epithelial markers connexins 26 and 43 was also increased, particularly in brain metastases. Despite the upregulation of epithelial markers in metastases, expression of mesenchymal markers vimentin and FSP1 was mostly unchanged or only slightly decreased. Furthermore, the switch in expression of E-cadherin to N-cadherin that is sometimes detected in EMT, was not found by our immunostaining. N-cadherin detection did not reveal a consistent pattern of expression in primary or metastastic tumors. We observed similar results in prostate cancer metastases; not only was E-cadherin expression increased but also expression inversely correlated with size of the metastasis, suggesting that a second EMT may occur in the ectopic site for tumor growth or to seed further metastases. In summary, we have observed an increased expression of epithelial markers and persistence of mesenchymal markers consistent with a partial MErT that may enable a second EMT at the metastatic site. Our results suggest that cancer cells continue to display phenotypic plasticity beyond the EMT that initiates metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3357. doi:10.1158/1538-7445.AM2011-3357