Cancer Cell Migration In 3D Collagen Gel Matrix System

Abstract

Cancer has long been one of the leading causes of death in the industrial world. The main reason for its high mortality is due to inefficient early detection which results in the spread of cancer cells to other distant sites in the body, via a process known as metastasis. Metastasis causes the dissemination of cancer cells and accounts for 90% of cancer-induced deaths, thus requiring better therapeutic treatments. The thesis examines a functional assay to study cancer cell invasive migration inside a three-dimensional (3D) collagen-I hydrogel, focusing on its micro-architecture and mechanics. First part of the project is the tuning of 3D collagen hydrogel to achieve varying fibre network structure and gel mechanical properties. Embedded in such collagen gels, breast cancer cells were tracked using live confocal imaging followed by quantitative 3D cell track analysis. The second part evaluated drug effects on cell migration using the model. Pharmacological inhibitions of cell-activated collagen matrix degradation and cytoskeletal reorganization reduced cell movement speed and directionality. Interestingly, the drug effects depended on the matrix micro-structure and elasticity. The study found that tissue mechanics is important in anti-migratory cancer drug assays, and incorporated ECM factors in interpreting results of drug assays.