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Abstract
Early detection of breast cancer is associated with a high survival rate of 99%; however, this rate decreases significantly (32%) once the cancer has metastasized. Unfortunately, current methods for detecting metastatic breast cancer are limited, and metastasis will not be identified until after the disease has spread. To enhance diagnostic capabilities, a deeper understanding of the biological mechanisms driving metastasis is urgently needed. One hallmark of metastasis is the epithelial-to-mesenchymal transition, during which cancer cells shift from an epithelial phenotype, characterized by a cuboidal shape and strong adhesion to the basement membrane, to a more elongated, mesenchymal phenotype. This transition in the cells reflects a tradeoff between cellular proliferation and invasiveness. While two-dimensional cell morphology (i.e. cell shape) has been identified as a quantifiable indicator of cell function, debate remains on which cellular structures are key to migration and invasion from the primary tumor. In this study, eight mammary cell lines, including five triple-negative breast cancer lines, a particularly aggressive subtype, were analyzed to produce a comprehensive profile of cancer cell behavior. Morphological features were compared with dynamic cellular activities like proliferation, migration, andcell-to-cell connectivity. This work employs a quantitative approach, using an impedance-based assay forreal-time analysis of proliferation and migration, offering improvements over traditional methods. High-throughput imaging and computational analysis were used to extract and quantify morphological features of the cells and their nuclei. The analysis revealed adiverse spectrum of morphological traits and aggressive behaviors across all cell lines. Overall, cell morphology was linked to behaviors such as migration, although the relationship was more complex and abstract than previously hypothesized. The findings from this work offer new insights into the cellular traits that influence breast cancer metastasis and establish a scalable framework for evaluating cancer cell behavior. By integrating detailed morphological and biophysical profiling with minimal sample input, this study contributes to the development of more efficient and clinically applicable investigative tools.