Investigating the role of oncofetal chondroitin sulfate in cancer biology and optimizing rVAR2 technology for cancer
department or school: Medicine, Faculty of
department or school: Pathology and Laboratory Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Wang, Chris Kedong
issued: 2022-04-30T07:00:00Z
issued: 2021
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Chondroitin sulfate (CS) is a glycosaminoglycan that can be attached to membrane proteins on the cell surface to form chondroitin sulfate proteoglycans (CSPG). CSPGs are highly expressed in the placenta and associated with the ability of the placenta to maintain a high rate of proliferation, angiogenesis, as well as invasion of the uterine tissue. CSPG alterations are also described in cancers and have been associated with progression and poor patient outcomes. Our lab has discovered that placenta and cancer cells express a common CS modification named oncofeatal CS (ofCS) that can be detected by the malarial lectin VAR2CSA. Using recombinant VAR2 proteins (rVAR2), we developed a new technology to detect and target solid tumors. As a component of this technology, the effect of rVAR2 on cancer cells as well as its fate inside the cancer cells needs to be established. Therefore, I hypothesized that rVAR2 binding to cancer cells would affect intracellular signaling pathways and cellular behavior. I aspired to support the development of the rVAR2 technology through three research aims: 1) Investigate the effects of rVAR2 binding to cancer cells. I showed that rVAR2 binding induced NF-κB pathway activation and cytokine expression. 2) Characterize the cellular fate of rVAR2 after binding to cancer cells. I established that rVAR2 internalize though different pathways into the early endosomes without reaching lysosomes. 3) Establishing an rVAR2-based exosome-detection strategy. I evaluated rVAR2 as a tool to isolate cancer derived exosomes and showed its limitation. Overall, the data generated in my research have advanced our knowledge on ofCS in cancer biology and informed ongoing rVAR2 based therapeutic development.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/78012
note: Investigating the role of oncofetal chondroitin sulfate in cancer biology and optimizing rVAR2 technology for cancer by Chris Kedong Wang B.Sc., University of British Columbia, 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY In THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pathology and Laboratory Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2021 © Chris Kedong Wang, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Investigating the role of oncofetal chondroitin sulfate in cancer biology and optimizing rVAR2 technology for cancer submitted by Chris Kedong Wang in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pathology and Laboratory Medicine Examining Committee: Mads Daugaard, Associate Professor, Urologic Sciences, UBC Supervisor Pauline Johnson, Professor, Microbiology & Immunology, UBC Supervisory Committee Member Vincent Duronio, Professor, Respiratory Medicine, UBC University Examiner Shyh-Dar Li, Professor, Pharmaceutical Sciences, UBC University Examiner Additional Supervisory Committee Members: Catherine Pallen, Professor Emeritus, Pathology and Laboratory Medicine, UBC Supervisory Committee Member Kevin Bennewith, Associate Professor, Pathology and Laboratory Medicine, UBC Supervisory Committee Member Alexander Wyatt, Assistant Professor, Urologic Sciences, UBC Supervisory Committee Member iii Abstract Chondroitin sulfate (CS) is a glycosaminoglycan that can be attached to membrane proteins on the cell surface to form chondroitin sulfate proteoglycans (CSPG). CSPGs are highly expressed in the placenta and associated with the ability of the placenta to maintain a high rate of proliferation, angiogenesis, as well as invasion of the uterine tissue. CSPG alterations are also described in cancers and have been associated with p…
has type: Thesis/Dissertation
date issued: 2021-05
is shown at: 10.14288/1.0396985
language: eng
degree discipline: Pathology and Laboratory Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/78012