Inhibition of hepatocellular carcinoma invasion by suppression of claudin-10 in HLE cells
Open Access
- 1 November 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 6 (11), 2858-2867
- https://doi.org/10.1158/1535-7163.mct-07-0453
Abstract
Previously, we showed that down-regulation of claudin-10 (CLDN-10) in hepatocellular carcinoma is associated with prolonged disease-free survival after curative surgery. Claudins are important tight junction components. Increasing evidence shows that claudins are involved in cancer progression but each member of claudins is specifically expressed in a variety of malignancies. The biological role of CLDN-10 in hepatocellular carcinoma is unexplored. In the current study, we investigated the CLDN-10 function in two different hepatocellular carcinoma cell lines by in vitro assays with the CLDN-10 overexpression and small interfering RNA–mediated knockdown transfectants. We observed that overexpression of CLDN-10 conferred malignant phenotypes to hepatocellular carcinoma cells, Hep3B, which lack CLDN-10 expression, by promoting cancer cell survival, motility, and invasiveness. More importantly, matrix metalloproteinase 2 (MMP2) was up-regulated. Increase in mRNA transcription and protein expression of membrane type 1-MMP (MT1-MMP) was also observed in the CLDN-10 transfectants, where MT1-MMP was a protease shown to promote intrahepatic metastasis in hepatocellular carcinoma in our earlier study. In addition, CLDN-1, CLDN-2, and CLDN-4 was up-regulated in CLDN-10 overexpression transfectants, indicating that the expression of CLDN-10 in cancer cells might affect the expression levels of its family members. On the contrary, small interfering RNA–based knockdown of CLDN-10 in HLE, an invasive cell line with high level of CLDN-10 expression, abolished invasion and strongly decreased activation of MMPs and claudin members expression. These findings showed that CLDN-10 is functionally involved in hepatocellular carcinoma invasion and is a potential target for hepatocellular carcinoma therapy. [Mol Cancer Ther 2007;6(11):2858–67]Keywords
This publication has 25 references indexed in Scilit:
- Uncommon tumors and exceptional therapies: paradox or paradigm?Molecular Cancer Therapeutics, 2007
- DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinomaCarcinogenesis: Integrative Cancer Research, 2007
- Atypical localization of membrane type 1‐matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinomaMolecular Carcinogenesis, 2007
- Claudin Proteins in Human Cancer: Promising New Targets for Diagnosis and TherapyCancer Research, 2005
- Claudins upregulation in human colorectal cancerFEBS Letters, 2005
- Loss of claudin‐1 expression in tumor‐associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasmsJournal of Cutaneous Pathology, 2005
- Claudin-1 regulates cellular transformation and metastatic behavior in colon cancerJCI Insight, 2005
- Quantitative RT‐PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesisThe Journal of Pathology, 2003
- Tight junction proteinsProgress in Biophysics and Molecular Biology, 2002
- Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomasHepatology, 2001