Effects of chemically EGFR targeting on non-targeted physical cell behaviors in 2D and 3D microfluidic cultures of invasive and non-invasive breast cancer cell lines

Abstract

Cancer development comprehends changes in cell structural and physical states. Cancer cells are softer than normal cells, produce higher contractile forces, and migrate more easily. While chemotherapy, targets proteins involved in biological behaviors, it may affect cell physicomechanical state due to the interconnections among signaling pathways. Here we treated non-invasive and invasive breast cancer cell lines by targeting EGRF which modulates major biological behaviors. We quantified migration potential of cancer cells in a microfluidic device, and evaluated expression of proteins associated with physical behaviors. Results indicated significant alterations in physical behaviors, with a higher impact on invasive cells. The anti-cancer synergy between biological and physical behaviors was shown by decreasing actin, vinculin, and myosin II content and altered distribution, limiting cell invasion in 3D collagen structure, accompanied by decreasing cell viability and vimentin expression as the EMT biomarker. The center point of changes in physical behaviors was in cytoskeletal remodeling by chemical treatment, potentially through lower contractile force generation and less development of focal adhesions and stress fibers. The synergy between physical and chemical pathways can be used in enhancing anti-cancer drug efficacy.

Keywords: Cancer; Cell migration; Cytoskeleton alteration; Invasion; Microfluidics.