Next Article in Journal
Dose- and Ion-Dependent Effects in the Oxidative Stress Response to Space-Like Radiation Exposure in the Skeletal System
Next Article in Special Issue
TGF-β-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases
Previous Article in Journal
Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice
Previous Article in Special Issue
A Central Bioactive Region of LTBP-2 Stimulates the Expression of TGF-β1 in Fibroblasts via Akt and p38 Signalling Pathways
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(10), 2119; doi:10.3390/ijms18102119

Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells

1
Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria
2
Institute for Clinical Chemistry, Medical Faculty Mannheim, University of Heidelberg, University Hospital Mannheim, 68167 Mannheim, Germany
3
Molecular Hepatology Section, Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg Mannheim, 68167 Mannheim, Germany
4
GenXPro GmbH, 60438 Frankfurt am Main, Germany
5
Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Received: 21 August 2017 / Revised: 15 September 2017 / Accepted: 15 September 2017 / Published: 10 October 2017
(This article belongs to the Special Issue TGF-beta Family in Fibrosis and Cancer)
View Full-Text   |   Download PDF [4262 KB, uploaded 12 October 2017]   |  

Abstract

The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis of hepatocellular carcinoma (HCC). The identification of molecular mechanisms involved in the transmigration of malignant hepatocytes through the endothelial barrier is of high relevance for therapeutic intervention and metastasis prevention. In this study, we employed a model of hepatocellular transmigration that mimics vascular invasion using hepatic sinusoidal endothelial cells and malignant hepatocytes evincing a mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-β. Labelling of respective cell populations with various stable isotopes and subsequent mass spectrometry analyses allowed the “real-time” detection of molecular changes in both transmigrating hepatocytes and endothelial cells. Interestingly, the proteome profiling revealed 36 and 559 regulated proteins in hepatocytes and endothelial cells, respectively, indicating significant changes during active transmigration that mostly depends on cell–cell interaction rather than on TGF-β alone. Importantly, matching these in vitro findings with HCC patient data revealed a panel of common molecular alterations including peroxiredoxin-3, epoxide hydrolase, transgelin-2 and collectin 12 that are clinically relevant for the patient’s survival. We conclude that hepatocellular plasticity induced by TGF-β is crucially involved in blood vessel invasion of HCC cells. View Full-Text
Keywords: hepatocellular carcinoma; TGF-β; transendothelial migration; SILAC; proteomics; bioinformatics hepatocellular carcinoma; TGF-β; transendothelial migration; SILAC; proteomics; bioinformatics
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Koudelkova, P.; Costina, V.; Weber, G.; Dooley, S.; Findeisen, P.; Winter, P.; Agarwal, R.; Schlangen, K.; Mikulits, W. Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells. Int. J. Mol. Sci. 2017, 18, 2119.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top