Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.

Cell Death & Disease
Francesco DituriGianluigi Giannelli

Abstract

Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting ca...Continue Reading

References

May 15, 1994·Archives of Biochemistry and Biophysics·B L SchumacherK E Kuettner
May 7, 1998·Journal of Biomedical Materials Research·G D JayC J Cha
Sep 17, 2004·Journal of Cellular Biochemistry·Anne-Marie HeegaardKarina Lishmann Nielsen
Oct 20, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Carlo BergaminiGianluigi Giannelli
Oct 31, 2007·Arthritis and Rheumatism·Gregory D JayMatthew L Warman
Mar 6, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emilia FransveaGianluigi Giannelli
May 29, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cédric CoulouarnSnorri S Thorgeirsson
Dec 31, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Emilia FransveaGianluigi Giannelli
Aug 28, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Antonio MazzoccaGianluigi Giannelli
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Antonio MazzoccaGianluigi Giannelli
Sep 17, 2010·Cancer Chemotherapy and Pharmacology·Emilia FransveaGianluigi Giannelli
Jun 16, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Antonio MazzoccaGianluigi Giannelli
Mar 15, 2013·Science Translational Medicine·Merry Z C RuanBrendan H L Lee
Apr 26, 2014·World Journal of Gastroenterology : WJG·Bhavna RaniGianluigi Giannelli
Jul 24, 2014·International Journal of Cancer. Journal International Du Cancer·Joan FernandoIsabel Fabregat
Jan 22, 2015·Arthritis & Rheumatology·Elena KozhemyakinaAndrew B Lassar
Jan 30, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jean-Charles Nault, Augusto Villanueva
Jan 26, 2016·The FEBS Journal·Isabel FabregatUNKNOWN IT-LIVER Consortium
Apr 3, 2016·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Mar 23, 2017·Frontiers in Cell and Developmental Biology·Linda T Senbanjo, Meenakshi A Chellaiah
Nov 19, 2017·Current Protein & Peptide Science·Marco ArreseDaniel Cabrera
Jul 5, 2018·The New England Journal of Medicine·Ghassan K Abou-AlfaRobin K Kelley
Nov 19, 2018·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Joya E NahonMiranda Van Eck

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Datasets Mentioned

BETA
GSE54236

Methods Mentioned

BETA
electrophoresis
flow cytometry
immunodepletion
nuclear translocation

Software Mentioned

ImageJ

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