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

Détails

ID Serval
serval:BIB_8DF16729717A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling.
Périodique
Immunity
Auteur(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
Statut éditorial
Publié
Date de publication
2004
Volume
21
Numéro
4
Pages
491-501
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
28/11/2011 20:02
Dernière modification de la notice
08/05/2019 21:50
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