Marta Coric, VAMPIRE researcher attended the Angiogensis Gordon Research Conference, August 2015.
The conference took place in Newport, RI, USA where Marta presented a poster on Functonal insights into the tumour endothelial marker CLEC14A .
Functonal insights into the tumour endothelial marker CLEC14A
Coric M, Noy P, Zhuang X, van der Flier L, Bicknell R
Differential expression of proteins in the tumour vasculature compared to vessels in healthy tissue has identified several potential anti-cancer targets. Nevertheless many therapies targeting vasculature fail to achieve the same success in the clinic as they show in preclinical studies. This is possibly due to a poor understanding of individual protein biology and mechanisms of their function in the vasculature. CLEC14A is a novel tumour endothelial marker (TEM) highly expressed in a wide range of solid tumours, possibly because of its expression under low shear stress that is found in tumour vessels. Preclinical studies of antiangiogenic treatments targeting CLEC14A have shown promising results: Knock out of CLEC14A in mice impairs the tumour vascularization and slows tumour growth. Monoclonal antibody targeting the extracellular domain of CLEC14A also impairs tumour growth.
We have confirmed that CLEC14A introduction into HEK293T cells induces filopodia formation, but the mechanism is unknown. To investigate this further we have performed mass spectrometry analysis of the intracellular domain of CLEC14A binding partners and identified proteins important in regulation of the actin cytoskeleton in cell migration. These include myosin IIa, myosin IIb and moesin. Another interesting protein that couples to CLEC14A is clathrin heavy chain I involved in clathrin mediated endocytosis and vesicle trafficking. These results reveal a possible mechanism of CLEC14A signaling from the extracellular matrix to intracellular migration machinery and cytoskeleton.