ERA

Download the full-sized PDF of The Role of Platelet Derived Growth Factor Receptor in Neuroendocrine TumoursDownload the full-sized PDF

Analytics

Share

Permanent link (DOI): https://doi.org/10.7939/R3PK0792T

Download

Export to: EndNote  |  Zotero  |  Mendeley

Communities

This file is in the following communities:

Graduate Studies and Research, Faculty of

Collections

This file is in the following collections:

Theses and Dissertations

The Role of Platelet Derived Growth Factor Receptor in Neuroendocrine Tumours Open Access

Descriptions

Other title
Subject/Keyword
Platelet Derived Growth Factor Receptor
Neuroendocrine tumours
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Ko, Yi Man
Supervisor and department
McMullen, Todd (Surgery)
Examining committee member and department
Murray, David (Oncology)
McEwan, Sandy (Oncology)
Department
Department of Surgery
Specialization
Experimental Surgery
Date accepted
2014-10-03T11:48:03Z
Graduation date
2014-11
Degree
Master of Science
Degree level
Master's
Abstract
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.
Language
English
DOI
doi:10.7939/R3PK0792T
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
2014-11-15T08:24:09.557+00:00
Audit Status
Audits have not yet been run on this file.
Characterization
File format: pdf (PDF/A)
Mime type: application/pdf
File size: 3643295
Last modified: 2015:10:12 16:09:25-06:00
Filename: Ko_Yi Man_201409_MSc.pdf
Original checksum: 14a7c84765745b76cb5df093444c38e0
Activity of users you follow
User Activity Date