| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>CD248 </it>gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth.</p> <p>Methods</p> <p>Mice lacking the cytoplasmic domain of CD248 (CD248<sup>CyD/CyD</sup>) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248<sup>WT/WT</sup>).</p> <p>Results</p> <p>As compared to the response in CD248<sup>WT/WT </sup>mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248<sup>CyD/CyD </sup>mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248<sup>CyD/CyD </sup>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, CD248<sup>CyD/CyD </sup>fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1.</p> <p>Conclusions</p> <p>The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer.</p>
|
|---|
