Simultaneous single cell imaging of calcium signal dynamics in breast cancer and neural cells reveals communication in a model of brain metastasis

The brain provides a unique metastatic microenvironment for breast cancer cells, where calcium signaling dynamics play critical roles in both cancer cell behavior and normal brain function. Calcium signal-mediated communication between breast cancer and neural cells has not yet been demonstrated through selective activation of breast cancer cells at the single cell level. To address this, we combined neural matrices of differentiated human neural progenitor cells with breast cancer cells expressing spectrally distinct genetically encoded calcium indicators. Specific activation of breast cancer cells increased calcium signaling activity in neural matrices with distinct temporal and spatial characteristics. Neural matrices also remodeled the expression of calcium-sensitive transcription factor SOX2 in a manner dependent on proximity to breast cancer cells. This work is the first simultaneous single-cell assessment of calcium signaling dynamics between breast cancer cells and neural cells modelling interactions within the brain metastatic niche.