Abstract 539: Endosialin (TEM1) is a tumor stroma marker and receptor for the metastasis-related Mac-2 binding protein

Abstract

Abstract Endosialin is a heavily sialylated C-type lectin. It is a single transmembrane molecule that was identified by two independent studies as an angiogenic endothelial specific marker. However, recent high resolution confocal expression studies by our and other laboratories have revealed that Endosialin is not expressed by endothelial cells but instead by angiogenic blood vessel associated pericytes. Detailed tissue array-based expression profiling validated Endosialin as an oncofetal gene product of the mesenchymal lineage that is hardly detectable in normal tissues but abundantly expressed by tumor vessel-associated pericytes and tumor stromal fibroblasts (myofibroblasts). As such, Endosialin was not just identified as a marker of activated pericytes but based on its exclusive tumor-associated expression also as a novel therapeutic tumor stroma target. Cytokine induction experiments identified Endosialin as a major downstream target of TGFß stimulation. Cellular siRNA-based loss-of-function experiments unravelled a role of Endosialin in the regulation of mesenchymal cell adhesion, migration and proliferation. These findings prompted experiments aimed at identifying the extracellular ligand of Endosialin. Using Endosialin-Fc as an affinity probe, the metastasis associated molecule Mac-2BP/90K was identified as high affinity extracellular Endosialin ligand. As Endosialin, Mac-2BP/90K displays an exclusive tumor progression associated expression pattern. However, in contrast to the stromal expression of Endosialin, Mac-2BP/90K is strictly expressed by the tumor cell compartment. The mutually exclusive expression pattern suggests a repulsive interaction between Endosialin and Mac-2BP/90K which was confirmed in cellular experiments. Ongoing experiments are aimed at mechanistically studying the role of the Endosialin - Mac-2BP/90K interaction in controlling the crosstalk between the tumor cell and the stromal cell compartments during tumor progression and metastasis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 539.