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Int. J. Mol. Sci. 2014, 15(6), 9422-9458;

Novel Aspects of the Liver Microenvironment in Hepatocellular Carcinoma Pathogenesis and Development

Liver Cell Biology, Centenary Institute, Sydney, NSW 2050, Australia
Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
Author to whom correspondence should be addressed.
Received: 7 March 2014 / Revised: 13 May 2014 / Accepted: 14 May 2014 / Published: 27 May 2014
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer that is derived from hepatocytes and is characterised by high mortality rate and poor prognosis. While HCC is driven by cumulative changes in the hepatocyte genome, it is increasingly recognised that the liver microenvironment plays a pivotal role in HCC propensity, progression and treatment response. The microenvironmental stimuli that have been recognised as being involved in HCC pathogenesis are diverse and include intrahepatic cell subpopulations, such as immune and stellate cells, pathogens, such as hepatitis viruses, and non-cellular factors, such as abnormal extracellular matrix (ECM) and tissue hypoxia. Recently, a number of novel environmental influences have been shown to have an equally dramatic, but previously unrecognized, role in HCC progression. Novel aspects, including diet, gastrointestinal tract (GIT) microflora and circulating microvesicles, are now being recognized as increasingly important in HCC pathogenesis. This review will outline aspects of the HCC microenvironment, including the potential role of GIT microflora and microvesicles, in providing new insights into tumourigenesis and identifying potential novel targets in the treatment of HCC. View Full-Text
Keywords: cancer; liver; microenvironment; hepatocellular carcinoma cancer; liver; microenvironment; hepatocellular carcinoma

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Tu, T.; Budzinska, M.A.; Maczurek, A.E.; Cheng, R.; Di Bartolomeo, A.; Warner, F.J.; McCaughan, G.W.; McLennan, S.V.; Shackel, N.A. Novel Aspects of the Liver Microenvironment in Hepatocellular Carcinoma Pathogenesis and Development. Int. J. Mol. Sci. 2014, 15, 9422-9458.

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