The biological implication of cancer stem cells in hepatocellular carcinoma: a possible target for future therapy

Abstract

Recent studies indicated the importance of stem cells in cancer, including in hepatocellular carcinoma. The presence of the stem cells and cancer stem cells in liver diseases is associated with the initiation, maintenance, metastasis and chemoresistance. Since hepatocellular carcinoma is a heterogeneous disease with a wide variety of prognostic types, which may limit the efficiency of standardized therapy, the understanding of the source of the cancer, alteration in important molecular signaling pathways and interaction between cancer cells and other cells types will be important in defining future, tailored treatment strategies.

Keywords::

• cancer stem cells
• drug resistance
• hepatocellular carcinoma
• microenvironment
• stem cells

Acknowledgement

The authors are grateful to Beatrice Anfuso and all the fellows of FIF for their support.

Financial & competing interests disclosure

CHCS was supported by a fellowship from Fondazione Italiana Fegato (FIF) and Fondazione Aldo Duca of the University of Trieste. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Hepatocellular carcinoma (HCC) accounts for around 90% of all cases of primary liver cancer, one of the most common neoplasms in the world.

• • Cancer stem cell (CSC) is associated with the initiation, maintenance and drug resistance in cancer. The CSC identification in HCC is based on the presence of CSC markers CD133, CD90, EpCAM, ALDH, CD24, OV6 and CD13, the capacity of spherical colony formation, and the isolation of side population.

• • The CSC activation arises from dysregulation in the oncogenic and developmental pathways, including Wnt/β-catenin, TGFβ, Notch and Hedgehog, leading to the tumorigenicity and invasion of the cells.

• • The CSC population has the intrinsic capacity to excrete chemotherapies and maintain the chemoresistance, in particular due to the activity of the ABCG2 protein.

Notes