The fibrotic microenvironment as a heterogeneity facet of hepatocellular carcinoma

Fibrogenesis & Tissue Repair
Krista Rombouts, Vinicio Carloni

Abstract

It has long been recognized that hepatocellular carcinoma heterogeneity arises from variation in the microenvironment or from genomic alteration. Only recently it has become clear that non-genetic alterations, such as cytoskeletal rearrangement, protein localization and formation of protein complexes, are also involved in generating phenotype variability. These proteome fluctuations cause genetically identical cells to vary significantly in their responsiveness to microenvironment stimuli. In the cirrhotic liver pre-malignant hepatocytes are continuously exposed to abnormal microenvironments, such as direct contact with activated hepatic stellate cells (HSCs) and extracellular matrix components. These abnormal environments can have pronounced influences on the epigenetic aspects of cells, translating into abnormal phenotypes. Here we discuss non-genetic causes of phenotypic heterogeneity of hepatocellular carcinoma, with an emphasis on variability of membrane protein complexes and transferred functions raising important implications for diagnosis and treatment.

References

Nov 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N A BegumG F Barnard
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·X Z GuoM W Büchler
Oct 3, 1999·International Journal of Cancer. Journal International Du Cancer·M NejjariJ Y Scoazec
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·K Simons, D Toomre
Jun 30, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·V CarloniP Gentilini
Oct 11, 2003·Journal of Gastroenterology and Hepatology·Kengo KanetakaSetsuo Hirohashi
Dec 17, 2003·Oncogene·Vinicio CarloniKodimangalam S Ravichandran
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Wenjun Guo, Filippo G Giancotti
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Sushmita Mukherjee, Frederick R Maxfield
Feb 9, 2005·Liver International : Official Journal of the International Association for the Study of the Liver·Maximilian Schöniger-HekeleChristian Müller
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jean S CampbellNelson Fausto
Dec 27, 2005·Current Opinion in Genetics & Development·Derek C Radisky, Mina J Bissell
Jul 20, 2006·Cancer Research·Sabine GesierichMargot Zöller
Aug 25, 2006·Nature Reviews. Cancer·Paraskevi A Farazi, Ronald A DePinho
Nov 15, 2007·Differentiation; Research in Biological Diversity·Jean S CampbellNelson Fausto
Nov 28, 2007·Annual Review of Pathology·Thea D Tlsty, Lisa M Coussens
Oct 17, 2008·The New England Journal of Medicine·Yujin HoshidaTodd R Golub
Dec 17, 2008·Nature Reviews. Cancer·Margot Zöller
Dec 26, 2008·The New England Journal of Medicine·Anne C Chiang, Joan Massagué
Aug 28, 2009·Trends in Cell Biology·María Yáñez-MóFrancisco Sánchez-Madrid
Nov 26, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Pau Sancho-BruRamón Bataller
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xu HouXuri Li
Jul 16, 2010·Developmental Cell·Mikala EgebladZena Werb
Jan 8, 2011·International Journal of Cancer. Journal International Du Cancer·Wenxiu ZhaoXiaomin Wang
Mar 3, 2011·Cancer Research·Alvin J X LeeCharles Swanton
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yong TaoChung-I Wu
Jul 19, 2011·Cancer Treatment Reviews·Sheng-Di WuXi-Zhong Shen
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xinxin GaoJin Zhang
Oct 14, 2011·The New England Journal of Medicine·Hashem B El-Serag
Oct 26, 2011·Nature Reviews. Gastroenterology & Hepatology·Yan LiJin-Xuan Hou
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Apr 20, 2012·Nature Reviews. Cancer·Andriy MarusykKornelia Polyak

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Citations

May 27, 2014·Cancer Letters·Antonio MazzoccaVinicio Carloni
Jan 9, 2014·Liver International : Official Journal of the International Association for the Study of the Liver·Vinicio CarloniKrista Rombouts
Dec 14, 2016·Annual Review of Pathology·Silvia AffoRobert F Schwabe
Feb 1, 2018·Digestive Diseases and Sciences·Julia Esperanza Torres-MenaJulio Isael Pérez-Carreón
Nov 8, 2017·Cancer·Faidon-Marios LaskaratosDalvinder Mandair
Sep 13, 2018·The Journal of Pathology. Clinical Research·Yihong WangMurray B Resnick
Nov 10, 2014·EMBO Reports·Michael W PickupValerie M Weaver
Aug 15, 2019·Rapid Communications in Mass Spectrometry : RCM·Koshi NagaiYoshihisa Tomioka
Aug 6, 2019·Frontiers in Cell and Developmental Biology·Lewis E ScottChristopher A Lemmon
Feb 22, 2017·International Journal of Molecular Sciences·Maryam Tahmasebi Birgani, Vinicio Carloni
Jun 5, 2017·Advanced Drug Delivery Reviews·Giuseppe MazzaKrista Rombouts

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Methods Mentioned

BETA
biopsies

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