Heterogeneity of Hepatic Cancer Stem Cells
Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality rate. It is a heterogeneous cancer with diverse inter- and intra-heterogeneity, also in terms of histology, prognosis, and molecular profiles. A rapidly growing evidence
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Heterogeneity of Hepatic Cancer Stem Cells Caecilia H. C. Sukowati
Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality rate. It is a heterogeneous cancer with diverse inter- and intra- heterogeneity, also in terms of histology, prognosis, and molecular profiles. A rapidly growing evidence has demonstrated that some HCCs, if not all, were caused by the activation of the cancer stem cells (CSC), a small population within the cancer that is responsible for the initiation and maintenance of cancer growth. Until now, various populations of hepatic CSC with more than ten different phenotypical protein markers, such as CD133, CD90, EpCAM, CD24, and CD13, have been identified and validated in xenotransplantation models. They are associated with risk factors, prognosis, chemo-resistance, and metastasis. This chapter summarizes available data on different hepatic CSC markers for the development of potential future therapy. Keywords Hepatocellular carcinoma · Liver cancer · Cancer stem cells · Tumor- initiating cells · Stem cells · CSC markers · CSC origin · Cancer heterogeneity · Chemo-resistance · Prognosis · Targeted therapy
4.1 Hepatocellular Carcinoma 4.1.1 Epidemiology and Risk Factors Recent epidemiology data Globocan 2018 of the International Agency for Research on Cancer—World Health Organization showed that liver cancer is the fifth most common cancer and the second most common cause of cancer-related death in men (Bray et al. 2018; Ferlay et al. 2019). The prognosis of this cancer is poor and the
C. H. C. Sukowati (*) Fondazione Italiana Fegato, Trieste, Italy Dipartimento di Area Medica, University of Udine, Udine, Italy e-mail: [email protected] © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_4
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geographical patterns in incidence and mortality are similar (Bray et al. 2013). Hepatocellular carcinoma (HCC) accounts for about 90% of liver cancer cases, with cirrhosis as the strongest underlying condition (El-Serag 2011). The global distribution of HCC is associated with the prevalence of its dominant risk factors. Infection of endemic hepatitis B virus (HBV) is the major cause of HCC in eastern Asia and sub-Saharan Africa for around 70%. In Europe and North America countries, hepatitis C virus (HCV) infection ranges from 50 to 70% while excessive alcohol consumption leading to alcohol steatohepatitis (ASH) contributes for around 20% of all cases (El-Serag 2011; Forner et al. 2012). Case-control studies from different countries report that chronic ethanol consumption is associated with an approximately twofold increased odds ratio for HCC (Ramadori et al. 2017). Besides the infection of hepatotropic viruses and alcohol, obesity and diabetes that commonly associated with non-alcoholic steatohepatitis (NASH) also increased the risk of HCC (Estes et al. 2018). Synergism between hepatitis vir
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