Format

Send to

Choose Destination
Immunity. 2004 Oct;21(4):491-501.

TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling.

Author information

1
Laboratory of Immunology, I. Medical Clinic, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Abstract

Alterations of TGF-beta signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-dependent IL-6 trans-signaling prevented tumor progression in vivo. Taken together, our data provide novel insights into TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-beta-dependent IL-6 trans-signaling.

PMID:
15485627
DOI:
10.1016/j.immuni.2004.07.020
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center