Universität zu Köln

Gullotti, Lucia, Czerwitzki, Jacqueline, Kirfel, Jutta, Propping, Peter, Rahner, Nils, Steinke, Verena, Kahl, Philip, Engel, Christoph ORCID: 0000-0002-7247-282X, Schuele, Roland, Buettner, Reinhard and Friedrichs, Nicolaus (2011). FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer. Lab. Invest., 91 (12). S. 1695 - 1706. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0307

Full text not available from this repository.

Abstract

Four and a half LIM domain protein-2 (FHL2) is a component of the focal adhesion structures and has been suggested to have an important role in cancer progression. This study analyses the role of FHL2 in peritumoural fibroblasts of sporadic and hereditary non-polyposis colorectal cancer (HNPCC). Tissue specimens of 48 sporadic and 49 hereditary colon cancers, respectively, were stained immunohistochemically for FHL2, transforming growth factor (TGF)-beta 1 ligand and alpha-SMA. Myofibroblasts at the tumour invasion front co-expressed alpha-SMA and FHL2. Sporadic colon cancer but not HNPCC cases showed a correlation between TGF-beta 1 expression of the invading tumour cells and FHL2 staining of peritumoural myofibroblasts. Overexpression of FHL2 in peritumoural myofibroblasts correlated to lymphatic metastasis in sporadic colon cancer but not in HNPCC. In cultured mouse fibroblasts, TGF-beta 1 treatment induced myofibroblast differentiation, stimulated FHL2 protein expression and elevated number of migratory cells in transwell motility assays, suggesting that FHL2 is regulated downstream of TGF-b. Physical contact of colon cancer cells and myofibroblasts via FHL2-positive focal adhesions was detected in human colon carcinoma tissue and in co-culture assays using sporadic as well as HNPCC-derived tumour cell lines. Our data provide strong evidence for an important role of FHL2 in the progression of colon cancers. Tumour-secreted TGF-beta 1 stimulates FHL2 protein expression in peritumoural fibroblasts, probably facilitating the invasion of tumour glands into the surrounding tissue by enhanced myofibroblast migration and tight connection of fibroblasts to tumour cells via focal adhesions. These findings are absent in HNPCC-associated colon cancers in vivo and may contribute to a less invasive and more protruding tumour margin of microsatellite instable carcinomas. Laboratory Investigation (2011) 91, 1695-1705; doi: 10.1038/ labinvest. 2011.109; published online 8 August 2011

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gullotti, Lucia UNSPECIFIED UNSPECIFIED UNSPECIFIED Czerwitzki, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Propping, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahner, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinke, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahl, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Engel, Christoph UNSPECIFIED orcid.org/0000-0002-7247-282X UNSPECIFIED Schuele, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-484402
DOI:	10.1038/labinvest.2011.109
Journal or Publication Title:	Lab. Invest.
Volume:	91
Number:	12
Page Range:	S. 1695 - 1706
Date:	2011
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0307
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ONLY PROTEIN FHL2; TRANSCRIPTIONAL COACTIVATOR FHL2; GROWTH-FACTOR-BETA; HUMAN BREAST; LIM-DOMAIN; DIFFERENTIATION; MYOFIBROBLAST; DEFICIENCY; ACTIVATION; INTERACTS Multiple languages Medicine, Research & Experimental; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48440