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

Details

Serval ID
serval:BIB_8DF16729717A
Type
Article: article from journal or magazin.
Collection
Publications
Title
TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling.
Journal
Immunity
Author(s)
Becker C., Fantini M.C., Schramm C., Lehr H.A., Wirtz S., Nikolaev A., Burg J., Strand S., Kiesslich R., Huber S., Ito H., Nishimoto N., Yoshizaki K., Kishimoto T., Galle P.R., Blessing M., Rose-John S., Neurath M.F.
ISSN
1074-7613 (Print)
ISSN-L
1074-7613
Publication state
Published
Issued date
2004
Volume
21
Number
4
Pages
491-501
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Keywords
Animals, Blotting, Western, Colonic Neoplasms/immunology, Colonic Neoplasms/metabolism, DNA-Binding Proteins/immunology, DNA-Binding Proteins/metabolism, Disease Models, Animal, Disease Progression, Endoscopy, Digestive System, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Interleukin-6/immunology, Interleukin-6/metabolism, Intestinal Mucosa/immunology, Intestinal Mucosa/metabolism, Mice, Mice, Knockout, Mice, Transgenic, Protein-Serine-Threonine Kinases, Receptors, Interleukin-6/immunology, Receptors, Interleukin-6/metabolism, Receptors, Transforming Growth Factor beta/genetics, Receptors, Transforming Growth Factor beta/immunology, Recombinant Fusion Proteins/immunology, Recombinant Fusion Proteins/metabolism, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Signal Transduction/physiology, T-Lymphocytes/immunology, Trans-Activators/immunology, Trans-Activators/metabolism, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/immunology
Pubmed
Open Access
Yes
Create date
28/11/2011 19:02
Last modification date
20/08/2019 14:51
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