जर्नल ऑफ़ मॉलिक्यूलर बायोमार्कर एंड डायग्नोसिस

Hepatitis-C Virus Increases Tumorigenic Potential of Hepatocellular Carcinoma (HCC) Cells by Expanding an Aldehyde Dehydrogenase 1 (ALDH1) Positive Stem Cell Like Population

Abstract

Abdellah Akil, Nabeel Alzahrani, Brahim Bouchrif, Mohammed Zahid Mustafa and Gaith Wedeh

Hepatitis C virus (HCV) is a major risk factor for chronic liver disease and hepatocellular carcinoma (HCC), the third-deadliest cancer. Despite extensive research efforts, the relationship between HCV and liver cancer stem cells (LCSCs) is still largely unknown. Our current study demonstrates that the continued expression of HCV significantly increased the expression of aldehyde dehydrogenase 1 (ALDH1) as well as the percent of ALDH1 positive liver cells (ALDH1+ cells), which is associated with increased steady-state level of CSC-like population. Furthermore, this continued expression of HCV in ALDH1+ cells induces the enhancement of cancer cell growth in vitro and is accompanied by a significant increase in xenograft tumor growth in vivo. Indeed, the ALDH1+ cells with continued expression of HCV were less vulnerable to treatment than normal ALDH1+ cells. Our results showed that HCV is capable of enhancing stem cell–like signatures and suggested the existence of a hierarchical organization in liver cell lines bearing tumorigenic potential in the order of HCV+/ALDH+> HCV-/ALDH+.