Expression of EpCAM Increases in the Hepatitis B Related and the Treatment-Resistant Hepatocellular Carcinoma

Osamu Kimura,Eiji Kakazu,Masashi Ninomiya,Takayuki Kogure,Yasuteru Kondo,Tooru Shimosegawa,Tatsuki Morosawa,Tomoaki Iwata

doi:10.1155/2014/172913

Abstract

Increasing evidence supports the important role of cancer stem cells (CSCs). Many reports suggest that epithelial cell adhesion molecule (EpCAM) is a useful marker for cancer stem cells in hepatocellular carcinoma (HCC). To elucidate the mechanisms of cancer stem cells, the development of specific molecular targeted drugs has become very important. In the present study, we examined the EpCAM expression pattern and its characteristic expression in resected HCC. We studied the drug resistance of EpCAM expression cells. EpCAM expression was detected significantly more frequently with hepatitis B virus (HBV) than with other etiologies. In HCC resection patients who had received prior treatment (transcatheter arterial embolization or hepatic arterial infusion chemotherapy), EpCAM was strongly expressed. In particular, very strong expression was observed after hepatic arterial infusion chemotherapy. The PLC/PRF/5 human HCC cell line expressed bimodal EpCAM, and EpCAM-positive cells had CSC cell potency. The EpCAM expression in EpCAM-positive cells increased significantly by treatment with cisplatin. EpCAM-positive cells showed better viability than EpCAM-negative cells when treated with ciplatin. Collectively, our results suggest that cancer stem cells are highly expressed in hepatitis B and have potential anticancer drug resistance.

Highlights

Worldwide, hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer [1] in human; it is the second most frequent cause of cancer death
Significant difference in the clinical profiles, except age and ALT, was not accepted (Table 1), because cancer occurs in hepatitis B virus (HBV) patients earlier than in those with other etiologies, and [non-B, non-C (NBNC) hepatitis] patients had relatively normal livers
epithelial cell adhesion molecule (EpCAM) was expressed at the regenerating region in normal hepatocytes (Figure 1(a))

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer [1] in human; it is the second most frequent cause of cancer death. In the early stages of hepatocellular carcinoma, when patients still maintain a hepatic functional reserve, local treatment such as hepatic resection or radiofrequency ablation is relatively effective [2]; many patients have repeated recurrence and died. There have been many studies [7,8,9] about cancer stem cells. The role of a relatively small fraction with potent growth potential, so-called cancer stem cells (CSCs), in tumorigenicity has been emerging. If CSCs survive treatment with anticancer drugs, a small number of cancer stem cells can grow again, acquiring the ability to resist anticancer drugs. The development of a treatment with a molecular mechanism for cancer stem cells is important

Methods

Results

Conclusion