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Updated: Mar 13, 2026
Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors
Published on: May 17, 2024
Neuroendocrine tumour morphology and platelet derived growth factor receptor alpha expression
Ana Lopez-Campistrous1, Yi Man Ko1, Melinda Wuest2
1Department of Surgery, University of Alberta, Edmonton, AB, Canada.
Abstract:
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.
Insights
Platelet-derived growth factor receptor alpha (PDGFRA) promotes metastasis and vascularization in neuroendocrine tumors by activating Akt and MAP kinase pathways. Targeting PDGFRA may offer a new theranostic approach for gastrointestinal neuroendocrine tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Gastrointestinal neuroendocrine tumors (GEP-NETs) frequently metastasize, limiting curative treatment options.
- Platelet-derived growth factor receptor alpha (PDGFRA) is overexpressed in metastatic GEP-NETs and is a target in clinical trials.
- Mechanistic studies on PDGFRA signaling in neuroendocrine tumors are lacking.
Purpose of the Study:
- To investigate the role of PDGFRA signaling in neuroendocrine tumor cell lines (BON-1 and QGP-1).
- To elucidate the downstream signaling pathways affected by PDGFRA.
- To assess the impact of PDGFRA on tumor growth and vascularization in vivo.
Main Methods:
- Utilized BON-1 and QGP-1 neuroendocrine cell lines.
- Examined colony formation, migration, and proliferation.
- Assessed Akt and MAP kinase pathway activation.
- Evaluated xenograft models for tumor growth, vascularization (CD31, vessel density), and PDGFRA expression.
Main Results:
- PDGFRA overexpression increased colony formation and migration in vitro, without significantly affecting proliferation.
- PDGFRA signaling activated Akt and MAP kinase pathways.
- PDGFRA expression in xenografts enhanced tumor vascularization, mimicking NET vascularity.
- PDGFRA significantly increased QGP-1 xenograft tumor size, but not BON-1 xenograft tumor size.
Conclusions:
- PDGFRA plays a significant role in promoting metastatic phenotypes and vascularization in neuroendocrine tumors.
- Activation of Akt and MAP kinase pathways mediates PDGFRA's effects.
- Divergent in vivo responses suggest cell-specific differences in MAPK pathway activation.
- Targeting PDGFRA presents a potential theranostic strategy for GEP-NETs.
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