The Role of Platelet Derived Growth Factor Receptor in Neuroendocrine Tumours

  • Author / Creator
    Ko, Yi Man
  • Neuroendocrine tumours (NETs) are composed of a broad family of tumours that develop from neuroendocrine cells dispersed throughout the body. The most common of which are carcinoid and pancreatic NETs. While NETs are relatively rare, the estimated incidence of NETs in the United States is increasing since the 1970s. Prognosis following complete surgical resection for local-regional disease is quite favorable. However, most patients present with metastatic disease making curative resection unlikely. Currently, there are limited therapeutic options in the setting of metastatic disease. NETs are highly vascular and angiogenesis plays an important role in tumour progression. Platelet-derived growth factor and its receptor (PDGF/PDGFR) is a class of growth factors which plays a significant role in angiogenesis. However, its role in NETs is not completely understood. The purpose of our study was to: i) assess the expression of PDGFR-α in human pancreatic neuroendocrine cell lines BON-1 and QGP-1 as well as in clinical specimens, ii) to determine the effect of PDGFR-α expression on cell migration and proliferation, and iii) to determine the effect of PDGFR-α expression on tumor growth in mouse xenograft model. We found that, although PDGFR-α is expressed on clinical specimens, neither BON-1 nor QGP-1 cell line express PDGFR-α. Therefore, stable BON-1 and QGP-1 constructs with inducible PDGFR-α expression were established to characterize its role in promoting tumour metastasis in NETs. The activation of PDGFR-α in BON-1 enhanced its migratory potential and the transformed phenotype can be reversed by selective PDGFR-α blockade. For both BON-1 and QGP-1, PDGFR-α expression increased tumor angiogenesis in vivo. Based on our results, tyrosine kinase inhibitors that target PDGFR, specifically the α-subunit, may be better suited to treating NETs.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Surgery
  • Specialization
    • Experimental Surgery
  • Supervisor / co-supervisor and their department(s)
    • McMullen, Todd (Surgery)
  • Examining committee members and their departments
    • Murray, David (Oncology)
    • McEwan, Sandy (Oncology)