QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 6 June 2006
doi: 10.1242/jcs.03011

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.03011v1 119/13/2727    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cat, B. Articles by Brenneisen, P. Search for Related Content PubMed PubMed Citation Articles by Cat, B. Articles by Brenneisen, P.

Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species

¹ Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, 40225 Düsseldorf, Germany
² Henkel KGaA, 40191 Düsseldorf, Germany

^* Author for correspondence (e-mail: PeterBrenneisen{at}web.de)

Accepted 30 March 2006

Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. Using an in vitro tumor-stroma model of skin carcinogenesis, we report here that tumor-cell-derived transforming growth factor ß1 (TGFß1) initiates reactive oxygen species-dependent expression of -smooth muscle actin, a biomarker for myofibroblastic cells belonging to a group of late-responsive genes. Moreover, protein kinase C (PKC) is involved in lipid hydroperoxide-triggered molecular events underlying transdifferentiation of fibroblasts to myofibroblasts (mesenchymal-mesenchymal transition, MMT). In contrast to fibroblasts, myofibroblasts secrete large amounts of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), resulting in a significant increase in the invasive capacity of tumor cells. The thiol N-acetyl-L-cysteine, the micronutrient selenite as well as selenoprotein P and the lipid peroxidation inhibitors -tocopherol and butylated hydroxytoluene significantly lower both the number of TGFß1-initiated myofibroblasts and the secretion of HGF, VEGF and IL-6, correlating with a diminished invasive capacity of tumor cells. This novel concept of stromal therapy, namely the protection of stromal cells against the dominating influence of tumor cells in tumor-stroma interaction by antioxidants and micronutrients, may form the basis for prevention of MMT in strategies for chemoprevention of tumor invasion.

Key words: Myofibroblast, Reactive oxygen species, Transforming growth factor ß, Tumor invasion, Tumor-stroma interaction

This article has been cited by other articles:

				N. Rocks, G. Paulissen, F. Quesada-Calvo, C. Munaut, M.-L. A. Gonzalez, M. Gueders, J. Hacha, C. Gilles, J.-M. Foidart, A. Noel, et al. ADAMTS-1 Metalloproteinase Promotes Tumor Development through the Induction of a Stromal Reaction In vivo Cancer Res., November 15, 2008; 68(22): 9541 - 9550. [Abstract] [Full Text] [PDF]

				C. Werth, D. Stuhlmann, B. Cat, H. Steinbrenner, L. Alili, H. Sies, and P. Brenneisen Stromal resistance of fibroblasts against oxidative damage: involvement of tumor cell-secreted platelet-derived growth factor (PDGF) and phosphoinositide 3-kinase (PI3K) activation Carcinogenesis, February 1, 2008; 29(2): 404 - 410. [Abstract] [Full Text] [PDF]

				A. K. Sasser, N. J. Sullivan, A. W. Studebaker, L. F. Hendey, A. E. Axel, and B. M. Hall Interleukin-6 is a potent growth factor for ER-{alpha}-positive human breast cancer FASEB J, November 1, 2007; 21(13): 3763 - 3770. [Abstract] [Full Text] [PDF]