Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

CD248 facilitates tumor growth via its cytoplasmic domain

Margarida Maia1234, Astrid DeVriese12, Tom Janssens12, Michaël Moons12, Rik J Lories5, Jan Tavernier34 and Edward M Conway126*

Author Affiliations

1 Vesalius Research Center, VIB, Herestraat 49, 9th floor, 3000 Belgium

2 Vesalius Research Center, K. U. Leuven, Herestraat 49, 9th floor, 3000 Belgium

3 Cytokine Receptor Laboratory, Department of Medical Protein Research, VIB, A. Baertsoenkaai 3, 9000 Ghent, Belgium

4 Cytokine Receptor Laboratory, Department of Biochemistry, Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium

5 Laboratory for Skeletal Development and Joint Disorders, Division of Rheumatology, K. U. Leuven, Herestraat 49, 3000 Belgium

6 Centre for Blood Research, Faculty of Medicine, Division of Hematology, University of British Columbia, 2350 Health Sciences Mall Vancouver, V6T 1Z3, Canada

For all author emails, please log on.

BMC Cancer 2011, 11:162  doi:10.1186/1471-2407-11-162

Published: 8 May 2011

Abstract

Background

Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth.

Methods

Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT).

Results

As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP)-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1.

Conclusions

The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer.

Keywords:
stromal fibroblast; suppressor; transgenic; endosialin; tumor endothelial marker