Universität zu Köln

Koliaraki, Vasiliki ORCID: 0000-0003-1694-6987, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Kollias, George (2015). IKK beta in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J. Exp. Med., 212 (13). S. 2235 - 2252. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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Abstract

The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKK beta in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKK beta is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKK beta-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-kappa B signaling and reduced expression of important NF-kappa B target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKK beta in driving inflammation and enabling carcinogenesis in the intestine.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koliaraki, Vasiliki UNSPECIFIED orcid.org/0000-0003-1694-6987 UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Kollias, George UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383730
DOI:	10.1084/jem.20150542
Journal or Publication Title:	J. Exp. Med.
Volume:	212
Number:	13
Page Range:	S. 2235 - 2252
Date:	2015
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-9538
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOUSE MODEL; KAPPA-B; COLORECTAL CARCINOGENESIS; INFLAMMATION; MICE; FIBROBLASTS; TNF; PROGRESSION; SURVIVAL; IMMUNITY Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/38373