"Molecular Characterization of CD133+ Cells as a Progenitor of Cancer Stem Cells in Hepatocellular Carcinoma"

Abstract

Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer, and it accounts for between 85% and 90% of these malignancies. HCC accounts for approximately 6% of all new cancer cases diagnosed, and due to its aggressiveness, it is the second most common cause of cancer mortality worldwide. The long term survival of postoperative HCC patients is unsatisfactory for the high incidence of recurrence. Chronic liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV) accounts for the majority of HCC cases. Egypt has the highest hepatitis C virus (HCV) prevalence worldwide, with14.7% prevalence in the 15–59 years age group. The cancer stem cells (CSC) are believed to be the cell populations that originate and maintain the tumor growth, induce chemo and radio resistance, and generate metastasis and relapses. CSCs possess stem cell- like properties, namely the ability to differentiate into multiple cell lineages and self-renew, and they are capable of regenerating a hierarchical structure containing various progenies in a similar fashion to normal stem cells. Both normal stem cells and CSCs are characterized by surface marker phenotype and possess similar molecular machinery responsible for self-renewal and differentiation. CD133 (prominin-1), a member of the transmembrane glycoprotein family, is a surface marker of the putative normal liver stem cells “oval cells”. Furthermore CD133 was the first surface marker identified in cells with characteristics of CSCs in HCC cell lines. In CSCs, miRNAs can regulate proliferation and self-renewal and promote differentiation to determine stem cell fates. In addition, miRNAs have been demonstrated to be an integral component of stem cell regulation, including normal stem cells (NSCs) and CSCs. Thus, the