The Impact of Astrocytes on Tumor Cell Dormancy Versus Proliferation in Brain Metastatic Breast Cancer Spheroids

While great strides have been made in the fight against cancer through primary, adjuvant, and palliative treatments, research has shown that cancer cells can stay dormant for extended periods of time, which also allows them to resist treatments. The signals that enable cancer cells to leave the dormant state and proliferate are currently not well understood, particularly in the context of brain metastatic breast cancer. Herein, we examined the impact of astrocytes (supporting cells of the brain) on the phenotype of brain metastatic breast cancer cells in a co-culture spheroid model. In this model, we employed MDA-MB-231Br brain metastatic breast cancer cells and C8-D1A mouse astrocytes in ratios of 1:1, 1:4, and 1:9 with cancer cells only serving as controls and cultured them for a period of 7 days. Among the 3 co-culture ratios tested, 1:4 and 1:1 culture conditions showed an increasing trend in proliferation as measured via spheroid area. The spheroid area for 1:9 condition decreased initially and stayed constant over the period of 7 days. Consistent with this observation, we found that the percentage of Ki67 (a proliferation marker) cells were significantly lower in the 1:9 condition compared to the other conditions. In future studies, we will further characterize the tumor cell phenotype, as well as their response to drug therapies. Such models provide useful tools to study cell-cell interactions and how such interactions impact the dormant versus proliferative phenotype. Ultimately, an improved understanding of dormancy may lead to the development of new therapeutic strategies.