Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Alison Allan

Abstract

Lung metastasis remains a leading cause of death in breast cancer patients. This study established an innovative 3D ex vivo pulmonary metastasis assay (PuMA) to test the hypothesis that the lung microenvironment promotes metastatic behaviour of whole population and stem-like ALDHhiCD44+ breast cancer cells. Following in vivo delivery of breast cancer cells to mice, lungs were excised, maintained in culture and imaged to observe breast cancer growth over time. We observed metastatic progression of breast cancer cells in the PuMA, most notably of ALDHhiCD44+ cells which progressed rapidly from single cells to multicellular colonies over 21 days relative to their ALDHloCD44- counterparts (p≤0.05). Although soluble lung-derived bFGF induced breast cancer cell proliferation in vitro, blocking bFGF in the PuMA showed only a trend towards inhibition of breast cancer cell growth. This model system will be valuable for elucidating the interaction between breast cancer cells and the lung during metastatic progression.


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