Understanding the recruitment, activation and function of pericytes during tumour angiogenesis

Angiogenesis is the process by which new blood vessels are formed from the pre-existing vasculature. As tumours are dependent on new blood vessels for their sustained growth, targeting the angiogenic vasculature is an attractive therapeutic option. For effective treatment it is desirable to target molecules that are selectively expressed on the tumour vasculature and it is for this reason that endosialin has been of recent interest. Endosialin (also known as CD248, tumour endothelium marker 1, TEM1) is a large transmembrane glycoprotein that was initially reported to be highly upregulated on tumour endothelial cells.

We have confirmed that endosialin is indeed overexpressed in breast cancers and gliomas. However, employing multiple fluorescent labelling of paraffin embedded tumour sections (Robertson et al., 2008) we have shown unequivocally that endosialin is not expressed on endothelial cells but on the closely associated perivascular cells or pericytes (MacFadyen et al, 2005; Simonavicius et al., 2008). Currently our studies are aimed at elucidating the function of endosialin and the mechanisms by which its expression is upregulated on angiogenic pericytes. Using a combination of in vitro, ex vivo and in vivo approaches we are focussing on the role of endosialin guiding and stabilising developing vessels and the therapeutic opportunity of targeting both endothelial cells and pericytes to develop more effective anti-angiogenic treatments.