Neuroendocrine tumour morphology and platelet derived growth factor receptor alpha expression

The strong propensity for lymphatic and distant metastases in gastrointestinal neuroendocrine tumours (GEP-NETS) often precludes cure for many patients. Platelet derived growth factor receptor alpha (PDGFRA) is commonly overexpressed in metastatic GEP-NETs and has been targeted in clinical trials, but there have been no direct mechanistic studies of PDGFRA cell signalling in neuroendocrine tumours. To address this gap, we examined the role of this tyrosine kinase receptor in the neuroendocrine cell lines BON-1 and QGP-1. We reveal increased colony formation and migratory potential without substantially altering proliferative capacity. This phenotype, similar to that seen in other PDGFRA cell line studies, appears to be mediated through Akt and MAP kinase pathways. Interestingly, in both xenograft models we also saw how PDGFRA expression induced striking similarities to the vascular nature of NET tumours, quantified through the vascular marker CD31 and vessel density. In terms of tumour growth, the presence of PDGFRA more than doubled the size of QGP-1 xenograft tumours but did not significantly alter BON-1 growth. The divergent in vivo phenotypes observed between BON-1 and QGP-1 xenografts likely reflect intrinsic differences in MAPK pathway activation. The creation of these new cell lines will aid in further studies to understand the potential role of targeting PDGFRA as a theranostic modality for patients with neuroendocrine tumours.