The underlying difference of metastatic and benign cancer cells in
configuring the fibre matrix to promote migration by long-distance cell
mechanics
Abstract
The progression of tumors is heavily influenced by mechanical properties
of their microenvironment. In this work, we designed micropatterned
models with varying distances and shapes to investigate the differences
between metastatic breast cancer cells MDA-MB-231 and non-metastatic
MCF-7 in reconfiguring the extracellular matrix to promote cell
migration induced by long-distance cell mechanics. Both cancer cells
were able to rearrange type I collagen fibres to form collagen threads,
in which MDA-MB-231 consistently migrated more rapidly than MCF-7,
ranging from matrix model with differently arrayed spacings to complex
polygonal models. MDA-MB-231 displayed higher capability of reorganizing
fibre bundles at longer distance (800 μm). Further looking for
differences in cellular mechanical mechanisms, siRNA knockdown
inhibiting either integrin β1 or Piezo1 decreased fibre assembly.
Metastatic MDA-MB-231 showed inhibited migration with integrin
knockdown, whereas scattered migration with Piezo1 knockdown indicating
cells losing distant mechanosensation. MCF-7 with reduced E-cadherin by
siRNA transfection showed less significant differences in migration
compared to MDA-MB-231 that didn’t express E-cadherin. MDA-MB-231
expressed little E-cadherin mRNA indicating mutagenetic change in
genome. In summary this work has explored the differences between
malignant and benign breast cancer cells, particularly in terms of fibre
matrix remodelling and cell migrations, along with significant
differences in E-cadherin expressions, of which had an important effect
on cell migration. The results of this study provide new research
approaches for therapeutic advances in breast cancer.