Quantitative Morphological Discrimination of Chemoresistant and Wild-Type Cancer Cells

Background: Morphological, qualitative observations allow pathologists to correlate the shape that cells acquire with the progressive, underlying neoplastic transformation they are experiencing. Indeed, cell morphology roughly scales with malignancy. A quantitative parameter for characterizing complex irregular structures is the Normalized Bending Energy (NBE). Methods: NBE provides a global feature for shape characterization correspondent to the amount of energy needed to transform the specific shape under analysis into its lowest energy state. We hypothesized that a chemotherapy resistant cancer cell line would experience a significant change in its shape, and that such a modification might be quantified by means of NBE parameterization. We checked out the usefulness of a mathematical algorithm to distinguish wild and 5-fluorouracil (5-FU)- resistant colon cancer HCT-8 cells (HCT-8FUres). NBE values, as well as cellular and molecular parameters, were recorded in both cell populations. Results: Results demonstrated that acquisition of drug resistance is accompanied by statistically significant morphological changes in cell membrane, as well as in biological parameters. Namely, NBE increased progressively; meanwhile, cells became more resistant to increasing 5-FU concentrations. Additionally, during a wound healing assay aimed to evaluate cancer cells motility, we observed that motility speed was found to be inversely correlated with solidity, a quantitative index of cell deformability and consequently may be considered a marker of acquired metastatic property. Conclusions: These data indicate how tight the relationships between morphology and phenotype are, and they support the idea of following cell transition toward a drug-resistant phenotype by means of morphological monitoring.