Abstract 1994: Cd44s is of functional importance for hepatocellular carcinoma (hcc) extra-hepatic metastases through activation of sdf-1a/cxcr4 axis

Abstract

Abstract Background: CD44 has been reported as a promoter of metastasis in several tumors, including HCC. In this study, we elucidated the critical role of CD44 in HCC metastasis, especially in distant metastasis as well as the underling mechanism. Methods: The expression of CXCR4, CD44 and their associated cellular signaling cascades, involving Akt and MAP Kinases, were determined by Western blotting. We also established CD44-deficient MHCC-97H cell lines by transfection with miRNA-CXCR4 plasmids and determined cell migration/invasion activity in a transwell assay.The prognostic value of CD44 and it's combination with CXCR4 was further evaluated. Results: HCC patients with higher CD44 have poor prognosis, including reduced disease-free and overall survival, and individuals with distinct metastasis have higher frequency expression of CD44. We found that expression of CD44 was positively related to metastatic potential of HCC cell lines, and modified cells with CD44high showed higher aggressiveness in vitro, and higher metastatic ability in vivo. Furthermore, the mechanism of CD44 improving the invasion activity of HCC cells was though the SDF-1a/CXCR4 axis. CD44 can activate the PI-3K/Akt pathway through binding HA, which can up-regulate the expression of CXCR4. CD44 combined with CXCR4 is a promising independent predictor of tumor recurrence and survival in hepatocellular carcinoma patients. CONCLUSIONS: CD44s is a potent predictor for extra-hapatic metastasis and overall survival of HCC patients. Our findings also provided evidence that the process of HA/CD44-induced CXCR4 expression is functional important for the invasiveness and metastasis of HCC. Therefore, the CD44-SDF-1α/CXCR4 system may be a new therapeutic target for treating HCC metastasis. Note: This abstract was not presented at the meeting. Citation Format: Wenwei Zhu, Lei Guo, Qinhai Ye. Cd44s is of functional importance for hepatocellular carcinoma (hcc) extra-hepatic metastases through activation of sdf-1a/cxcr4 axis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1994. doi:10.1158/1538-7445.AM2014-1994