Hepatocellular Cancer: Molecular Mechanisms, Diagnosis and Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 1655

Special Issue Editor


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Guest Editor
KU Leuven – University Hospital Leuven, 3000 Leuven, Belgium
Interests: liver dsease; translational research; hepatocellular cancer

Special Issue Information

Dear Colleagues, 

Liver cancer is a devastating disease with poor prognosis. Approximately 80% of HCCs arise in patients with a background of long-lasting chronic liver disease. In order to understand the pathogenesis of HCC, therefore, it is important to know what is happening in the chronically diseased liver. The regenerating liver is an ambient setting full of inflammation, stress and signal/cell interactions: a vivid and complex substrate in which  HCCs arise.              
Primary liver cancers are traditionally classified into hepatocellular carcinoma (HCC) and the less common but more aggressive cholangiocarcinoma (CCA), a cancer with cholangiocyte (also known as biliary epithelial cell, BEC) characteristics. A major obstacle in treating primary liver cancers is their enormous heterogeneity, forming a spectrum from pure HCC, through mixed and intermediate tumours, to pure CCA; the more cholangiocytic their characteristics, the more aggressive they are. During progression and in response to treatment, primary liver cancers can adapt and become resistant to treatment, often with an amplified cholangiocytic character. How HCC cells acquire cellular plasticity and how they shift phenotype is not known. Understanding these mechanisms is important because this will direct approaches to suppress the evolution of liver cancer into more aggressive forms.

In this Special Issue we would like to focus on the pathogenesis of hepatocellular cancer at the cellular and molecular levels, on the diagnosis and classification of liver cancer, and on potential treatment options.

Prof. Dr. Tania Roskams
Guest Editor

Manuscript Submission Information

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Keywords

  • primary liver cancer
  • liver cancer pathogenesis
  • liver cancer classification
  • liver cancer diagnosis
  • liver cancer treatment

Published Papers (1 paper)

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Research

28 pages, 21424 KiB  
Article
Influence of C60 Nanofilm on the Expression of Selected Markers of Mesenchymal–Epithelial Transition in Hepatocellular Carcinoma
by Malwina Sosnowska, Marta Kutwin, Katarzyna Zawadzka, Michał Pruchniewski, Barbara Strojny, Zuzanna Bujalska, Mateusz Wierzbicki, Sławomir Jaworski and Ewa Sawosz
Cancers 2023, 15(23), 5553; https://doi.org/10.3390/cancers15235553 - 23 Nov 2023
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Abstract
The epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire the ability to actively migrate via a change to the mesenchymal phenotype. This mechanism occurs in an environment rich in cytokines and reactive oxygen species but poor in nutrients. The aim [...] Read more.
The epithelial–mesenchymal transition (EMT) is a process in which epithelial cells acquire the ability to actively migrate via a change to the mesenchymal phenotype. This mechanism occurs in an environment rich in cytokines and reactive oxygen species but poor in nutrients. The aim of this study was to demonstrate that the use of a fullerene C60 nanofilm can inhibit liver cancer cell invasion by restoring their non-aggressive, epithelial phenotype. We employed epithelial and mesenchymal HepG2 and SNU-449 liver cancer cells and non-cancerous mesenchymal HFF2 cells in this work. We used enzyme-linked immunosorbent assays (ELISAs) to determine the content of glutathione and transforming growth factor (TGF) in cells. We measured the total antioxidant capacity with a commercially available kit. We assessed cell invasion based on changes in morphology, the scratch test and the Boyden chamber invasion. In addition, we measured the effect of C60 nanofilm on restoring the epithelial phenotype at the protein level with protein membranes, Western blotting and mass spectrometry. C60 nanofilm downregulated TGF and increased glutathione expression in SNU-449 cells. When grown on C60 nanofilm, invasive cells showed enhanced intercellular connectivity; reduced three-dimensional invasion; and reduced the expression of key invasion markers, namely MMP-1, MMP-9, TIMP-1, TIMP-2 and TIMP-4. Mass spectrometry showed that among the 96 altered proteins in HepG2 cells grown on C60 nanofilm, 41 proteins are involved in EMT and EMT-modulating processes such as autophagy, inflammation and oxidative stress. The C60 nanofilm inhibited autophagy, showed antioxidant and anti-inflammatory properties, increased glucose transport and regulated the β-catenin/keratin/Smad4/snail+slug and MMP signalling pathways. In conclusion, the C60 nanofilm induces a hybrid mesenchymal–epithelial phenotype and could be used in the prevention of postoperative recurrences. Full article
(This article belongs to the Special Issue Hepatocellular Cancer: Molecular Mechanisms, Diagnosis and Therapy)
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