Abstract 3319: CD44 standard isoform regulates the mesenchymal phenotype in hepatocellular carcinoma cells, and associates with a poor prognosis in patients.

Abstract

Abstract Purpose: Cancer stem cells (CSCs) in many tumors have been identified using CD44, either individually or in combination with other markers and are involved in tumor progression and metastasis. Epithelial-mesenchymal transition (EMT) is known to induce cancer invasion, metastasis, and CSCs properties. However, the underlying molecular mechanisms which integrate EMT and CSCs properties remain largely unknown. In this study, we test the hypothesis that CSCs markers play an important role in regulating EMT in hepatocellular carcinoma (HCC). Experimental Design: The relationship between the CSCs markers and EMT markers was investigated in HCC cell lines. The EMT markers, invasive phenotype, the relevant transcriptional factors and signaling pathways induced by CD44 were examined in vitro. The clinicopathological importance of CD44 standard isoform (CD44s) expression was analyzed by an immunohistochemical analysis, and the correlation of CD44s and EMT markers was determined in 150 patients with hepatocellular carcinoma. Results: HCC cell lines with high CD44 expression showed decreased E-cadherin expression and increased vimentin expression. CD44s mRNA was dominant form of CD44 mRNA present in HCC cell lines with the mesenchymal phenotype. Overexpression of CD44s in HCC cells induced the mesenchymal phenotype and increased tumor cell invasion, whereas knockdown of CD44s in HCC cells led to loss the mesenchymal phenotype and decreased tumor cell invasion. CD44s expression was associated with E-cadherin low expression (P=0.039) and vimentin high expression (P<0.001). CD44s expression was related to a large tumor size (P=0.003), multiple tumors (P=0.032), and poor tumor differentiation (P=0.020), and a shorter disease-free (P=0.023) and overall survival (P=0.013) in patients with HCC. Conclusions: our study will be valuable for understanding the relationship between CSCs and EMT, and the identification of new treatment targets for future HCC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3319. doi:1538-7445.AM2012-3319