Molecular signalling and interactions in colon cancer stem cells
Author(s)
Primary Supervisor
Lam, Alfred
Gopalan, Vinod
Other Supervisors
Smith, Robert
Year published
2019-04
Metadata
Show full item recordAbstract
Colorectal cancer, the cancer of the inner lining of the large intestine, is the second most commonly diagnosed cancer in the aging Australian population. Many studies have shown that cancer stem cells, or formally referred to as tumour-initiating cells, are the key initiator of cancer and responsible for cancer relapse. The current study set out to widen the current understanding of colon cancer stem-like cell population and identify novel signalling targets in colon cancer stem cells. The current study was able to demonstrate that colon cancer cell lines SW48 and SW480 possess a stem-like subpopulation which is identifiable ...
View more >Colorectal cancer, the cancer of the inner lining of the large intestine, is the second most commonly diagnosed cancer in the aging Australian population. Many studies have shown that cancer stem cells, or formally referred to as tumour-initiating cells, are the key initiator of cancer and responsible for cancer relapse. The current study set out to widen the current understanding of colon cancer stem-like cell population and identify novel signalling targets in colon cancer stem cells. The current study was able to demonstrate that colon cancer cell lines SW48 and SW480 possess a stem-like subpopulation which is identifiable through high levels of the stemness marker ALDH1. Furthermore, this population of cells can survive in stem-like culture conditions and form spheroids representative of stem-like cells. Transforming growth factor beta (TGF-[beta]) is a multipurpose cytokine which plays a role in the regulations of biological responses and has been shown to play a key role in stemness maintenance through its involvement in the epithelial to mesenchymal transition. However, [its] role in colon cancer stem cells has not been widely studied. The current study found that prolonged exposure to TGF-[beta] within the microenvironment affects stem-like cell morphology, proliferation, invasion, expression of stemness markers and cancer-related genes. The tgf-[beta] growth factor is also known to play a role in inflammation and immune system regulation. The results of the current study indicate that TGF-[beta] growth factor treatment lowered the proliferation of colon cancer stem-like cells following exposure to cytotoxic compounds, increased sensitivity to chemotherapeutic drug treatment, reduced viability of stem-like cells following treatment with cytotoxic compounds and modified stem-like cell morphology.
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View more >Colorectal cancer, the cancer of the inner lining of the large intestine, is the second most commonly diagnosed cancer in the aging Australian population. Many studies have shown that cancer stem cells, or formally referred to as tumour-initiating cells, are the key initiator of cancer and responsible for cancer relapse. The current study set out to widen the current understanding of colon cancer stem-like cell population and identify novel signalling targets in colon cancer stem cells. The current study was able to demonstrate that colon cancer cell lines SW48 and SW480 possess a stem-like subpopulation which is identifiable through high levels of the stemness marker ALDH1. Furthermore, this population of cells can survive in stem-like culture conditions and form spheroids representative of stem-like cells. Transforming growth factor beta (TGF-[beta]) is a multipurpose cytokine which plays a role in the regulations of biological responses and has been shown to play a key role in stemness maintenance through its involvement in the epithelial to mesenchymal transition. However, [its] role in colon cancer stem cells has not been widely studied. The current study found that prolonged exposure to TGF-[beta] within the microenvironment affects stem-like cell morphology, proliferation, invasion, expression of stemness markers and cancer-related genes. The tgf-[beta] growth factor is also known to play a role in inflammation and immune system regulation. The results of the current study indicate that TGF-[beta] growth factor treatment lowered the proliferation of colon cancer stem-like cells following exposure to cytotoxic compounds, increased sensitivity to chemotherapeutic drug treatment, reduced viability of stem-like cells following treatment with cytotoxic compounds and modified stem-like cell morphology.
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Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Medicine
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Subject
Colorectal cancer
Cancer stem cells
Transforming growth factor beta
Molecular signalling and interactions