Establishment of a novel system for the culture and expansion of hepatic stem-like cancer cells

Hepatocellular carcinoma (HCC) is a major primary liver malignancy in adults. Despite the progress made, the outcome of the treatment to this disease is less than satisfactory as the post therapy tumor recurrence is almost inevitable. Accumulating pieces of evidence have suggested that the recurrence is due to the existence of a subpopulation of the HCC cells that possess the properties of stem cells and are resistant to radiation and chemotherapy. It is therefore important to understand the characteristics of this subpopulation of HCC cells, and which requires the establishment of an in vitro system to study these stem-like cancer cells. However, despite extensive efforts, the progress in establishing such an in vitro system has been slow largely due to the lack of definitive biomarkers in the isolation and expansion of these cells. In order to successfully maintain and expand HCC CSCs, we first optimized the culture system. We establish a novel medium system that allows the culture and enrichment of these hepatic stem-like cancer cells from both hepatoma cells and human primary HCC cells. These cells exhibited typical stem cell properties, such as enhanced stem cell markers, gain of EMT properties and drug resistance, and more importantly, stronger tumor-initiating capabilities. The medium may help to establish an in vitro model for hepatic cancer stem cell (HCSC) studies, which may contribute to the development of novel cell therapies and new drugs for the treatment of HCC.