Are Biomechanical Changes Necessary for Tumor Progression? - The Impact of Cell Mechanics on Cancer Progression

Abstract

Biophysics established a new research area which described the progression of cancer from a materials science perspective. It has been know for a long time that malignant transformation is associated with significant changes in the cellular cytoskeleton. If the cytoskeleton's alterations are necessary for malignant transformation, they have to trigger biomechanical changes that impact cellular functions. In all cancers malignant neoplasia - uncontrolled growth, invasion into the surrounding tissue and metastasis occurs. Our results indicate that all these three phenomechanisms of malignancy require changes in the active and passive biomechanics of a tumor cell. Optical stretcher experiments with tumor cell lines and primary cells clearly show that malignant transformation causes cell softening for small deformations which correlates with an increased rate of proliferation compared to normal cells. However, tumor spheroids confined in agar gel proliferate until a gel stiffness of 104 Pa is exceeded which results in strain-hardening of cytoskeletal filaments at larger deformations. Furthermore, cell softening of the actin cortex can increase individual cell speed for lamellipodial motion of malignantly transformed fibroblasts and breast cancer cell lines. However, all cells can migrate and the motion of epithelial cells is mainly determined by their environment, whereas fibroblasts have the capability to move freely. Thus, it is the ability of single epithelial cells to overcome the tumor barrier to metastasize. The barrier that cells feel when they try to leave their cell compartment can be lowered by reducing cell adhesion. In breast tumor samples, small numbers of cells can be found that actively contract when laser light tries to stretch them. These could play a key role in metastasis because contraction can pre-strain and thus stiffen the cells to reduce adhesion sides to adjacent cells.