Karla Williams

Breast cancer has surpassed the incidence of lung cancer and is now the most prevalent form of cancer worldwide. Metastasis is a hallmark of cancer and is associated with the highest number of cancer-associated deaths. As metastatic disease is the primary cause of breast cancer patient death, this thesis is aimed to develop in vitro, ex ovo and in vivo models to study the different stages of breast cancer growth and metastasis. For this, we utilized the chick chorioallantoic membrane (CAM) model and developed models for studying: (i) breast cancer growth and angiogenesis, and (ii) organ specific breast cancer metastasis. The third part of the thesis optimizes the study of breast cancer invasion into the lymphatic system using an in vitro lymphatic invasion and in vivo mouse model whereby we focus on the role of invadopodia in mediating this process. The work described in this thesis demonstrates that bioluminescence imaging can be used to monitor breast tumor growth and response to therapeutic treatment in tumors xenografted onto the chick embryo CAM. Our work also shows the utility of the chick embryo model to study site-specific metastasis and evaluate therapeutic response in the metastatic setting. Finally, our model to monitor tumor cell invasion through a lymphatic endothelial barrier found that this process is in-fact mediated by invadopodia. Another important contribution of this thesis comes from the evaluation of metastatic lesions in the lymph node to contribute to lung tumor burden. Our work shows clear importance for lymph node metastatic dissemination in the contribution to metastatic lung disease and establishes the role of invadopodia in this process.

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