SELECTION AND CHARACTERIZATION OF MECHANORESILIENT BREAST CANCER CELLS

Abstract

Metastatic tumors always occur at the late cancer stages and are the main contributors to cancer-associated deaths. It is unclear whether the destructive mechanical deformations constantly encountered by circulating tumor cells (CTCs) are selecting any specific traits in those survivor CTCs. Additionally, a comprehensive understanding of the high capillary deformation-mediated alternations in metastatic cancer cells is still missing. In this thesis, I designed a microfluidic system to mimic the high mechanical deformation experienced by cancer cells during their blood-borne. I optimized a workflow to collect the survivor cells after such mechanical selection. This cancer subpopulation is termed “mechanoresilient (MR) cancer cells” in this study. We subsequently used this novel cancer subtype as an experimental model to study 1) factors that confer survival advantages to the cancer cells during the selection; 2) functional alternations brought by the mechanical stresses to this subpopulation; and 3) the clinical implications of such alternations.