Myeloid STAT3 promotes formation of colitis-associated colorectal cancer in mice.

Autor:	Pathria P; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Gotthardt D; Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria., Prchal-Murphy M; Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria., Putz EM; Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria., Holcmann M; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Schlederer M; Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria., Grabner B; Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria., Crncec I; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Svinka J; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Musteanu M; Spanish National Cancer Research Centre (CNIO) ; Madrid, Spain., Hoffmann T; Institute of Molecular Pathology IMP ; Vienna, Austria., Filipits M; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Berger W; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Poli V; Department of Molecular Biotechnology and Health Sciences; Molecular Biotechnology Center; University of Turin ; Italy., Kenner L; Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria., Bilban M; Medical University Vienna; Department of Medical and Chemical Laboratory Diagnostics ; Vienna, Austria ;, Casanova E; Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria., Müller M; Institute of Animal Breeding and Genetics; University of Veterinary Medicine Vienna ; Vienna, Austria., Strobl B; Institute of Animal Breeding and Genetics; University of Veterinary Medicine Vienna ; Vienna, Austria., Bayer E; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Mohr T; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria., Sexl V; Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria., Eferl R; Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2015 Jan 22; Vol. 4 (4), pp. e998529. Date of Electronic Publication: 2015 Jan 22 (Print Publication: 2015).
DOI:	10.1080/2162402X.2014.998529
Abstrakt:	Myeloid cells lacking STAT3 promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deleted STAT3 in murine myeloid cells (STAT3 Δm ) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3 Δm mice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3 Δm CRCs. Moreover, STAT3 Δm host mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lacking STAT3 control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3 Δm mice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3 Δm mice consistently activate STAT3 signaling which is implicated in immune evasion and might be a target to prevent tumor relapse.
Databáze:	MEDLINE
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