Innate and anti-cancer drug-induced morphological changes in the human breast cancer cell line MDA-MB-231

Abstract

Phenotypic changes in tumour cells is a well-established phenomenon and can happen either naturally or in response to a drug. Such changes in phenotype are often accompanied with changes in the behaviour of tumour cells, including growth, proliferation, as well as their migratory and invasive capacity. Phenotypic changes can, therefore, impact the aggressiveness of the tumour cell and dictate their metastatic potential. Thus, it is of utmost importance to fully understand and characterise phenotypic changes in tumour cells in order to better understand tumour progression and identify therapeutic targets. The research described in this thesis focused on morphological changes in the human breast cancer cell line, MDA-MB-231, arising from two conditions: a spontaneous, natural transformation that cells undergo, and a transformation induced by the gallium complex, tris(8-hydroxyquinolinato)gallium(III) [GaQ3]. Techniques utilised in this study included digital holographic microscopy, scanning electron microscopy, confocal microscopy, short tandem repeat profiling, migration and invasion wound healing assays, as well as Fourier transform infrared spectroscopy. It was found that whether the cell undergoes natural or drug-induced morphological changes, the changes in cell phenotypes are accompanied with functional changes, with the most significant functional change being a reduction in the cell’s invasive potential. Further, phenotypic changes that MDA-MB-231 cells may naturally undergo were likely to be induced by the release and uptake of extracellular vesicles. The findings of this thesis, therefore, have significant implications in understanding cancer metastasis, and opens new avenues for the intervention of possible anti-metastatic therapies.