TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling
Immunity. Bd. 21. H. 4. Cambridge, Mass.: Cell Press 2004 S. 491 - 501
Erscheinungsjahr: 2004
ISBN/ISSN: 1074-7613
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
Doi/URN: 10.1016/j.immuni.2004.07.020
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Inhaltszusammenfassung
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 si...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.» weiterlesen» einklappen
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DDC Sachgruppe:
Medizin
