Stemness and reprogramming in liver cancer

Hepatocellular carcinoma (HCC) is the most common and deadly cause of primary liver cancer. Although the incidence of HCC is highest in Asia and sub-Saharan Africa the steadily increasing incidence of HCC in traditionally low incidence regions such as Northern Europe and the United States constitutes a significant public health care problem. Cells with "stemness," or stem-cell properties, are referred to as cancer stem cells (CSC) or cancer-initiating cells. The concept that these cells rest at the apex of the cancer hierarchy is an evolving theme in cancer research. These cells are by definition primarily responsible for initiation and propagation of tumors as well as relapse after therapy, and they are therefore of major scientific interest. Several studies indicate that hepatocellular carcinomas that harbor phenotypic features of stem cells and progenitor cells constitute a subclass of therapeutically challenging cancers that are associated with a particularly poor prognosis. We recently showed that any hepatic lineage cell can be reprogrammed into CSC by activating diverse cell type-specific pathways. Furthermore, we identified common and cell of origin-specific phenotypic and genetic changes that accurately differentiated murine tumors according to their origin, providing an important tool to phenotypically classify morphologically diverse human primary liver cancer. These and more recent studies will be discussed in the presentation.