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Chen, Xuewei

University of British Columbia

Breast cancer is the most commonly diagnosed cancer globally, where around 34% of patients will develop metastatic breast cancer with only 22% survival rate over five years. Individuals who develop metastatic breast cancer patients have limited effective treatment options. To improve treatment options, a better understanding of metastatic disease is needed. Studies focused on understanding the process of tumor cell metastasis will result in improvements to our understanding of tumor metastasis and may identify novel disease drivers that can be drug targets. Here, this thesis aims to investigate tumor cell dissemination as regulated by small sub-cellular structures called invadopodia. Invadopodia are specialized actin-rich membrane protrusions that aid in tumor cell dissemination and invasion. Invadopodia have been shown to degrade the extracellular matrix to invade surrounding tissues and facilitate the entry and exit through blood vessels. We investigated the role of invadopodia in driving tumor cell invasion through a model of the lymphatic endothelium. Invadopodia were found to mediate this process and further investigation into invadopodia-based drivers of this process identified CCR7 as a mediator. CCR7 is a chemokine receptor that is known to home the dendritic cells to the lymph nodes, and has two endogenous ligands CCL19 and CCL21. In our model, tumor cells were responsive to CCL19 and this promoted invadopodia formation and increased invasion through a lymphatic endothelium model. Overall, this study has advanced our understanding of invadopodia-associated tumor cell dissemination via lymphatics, and provides insight into a mechanism of CCR7-mediated invadopodia invasion.

Text

2024-02-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/83880

Pharmaceutical Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/