Nuclear Deformability of Breast Cells Analyzed from Patients with Malignant and Benign Breast Diseases

Abstract

Breast cancer is a heterogeneous and dynamic disease, in which cancer cells are highly responsive to alterations in the microenvironment. Today, conventional methods of detecting cancer give a rather static image of the condition of the disease, so dynamic properties such as invasiveness and metastasis are difficult to capture. In this study, conventional molecular-level evaluations of the patients with breast adenocarcinoma were combined with in vitro methods on micropatterned poly(methyl methacrylate) (PMMA) biomaterial surfaces that deform cells. A correlation between deformability of the nuclei and cancer stemness, invasiveness, and metastasis was sought. Clinical patient samples were from regions of the breast with different proximities to the tumor. Responses at the single-cell level toward the micropatterned surfaces were studied using CD44/24, epithelial cell adhesion marker (EpCAM), MUC1, and PCK. Results showed that molecular markers and shape descriptors can discriminate the cells from different proximities to the tumor center and from different patients. The cells with the most metastatic and invasive properties showed both the highest deformability and the highest level of metastatic markers. In conclusion, by using a combination of molecular markers together with nuclear deformation, it is possible to improve detection and separation of subpopulations in heterogenous breast cancer specimens at the single-cell level.

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

“…The interaction between cells and materials is a fundamental issue in the fields of biomaterials and tissue regeneration. − Micropillar arrays provide a unique kind of topological surfaces to regulate cell-material interactions. − Cell nuclei undergo severe deformation on micropillar arrays with an appropriate dimension, which influenced cell behaviors . Nuclear deformation can also cause chromatin condensation and chromosome relocalization within the nucleus and alter gene expression of the cells. − It has been demonstrated that actomyosin and microtubule may synergistically regulate nuclear deformation and chromatin remodeling, finally modulating gene expression .…”