Mechanical control of breast cancer metastasis
Cancer metastasis occurs when cancer cells detach from the primary tumor and disseminate through the body either as single cells or collectively. In a paper just published in Nature Cell Biology, researchers from the Center for Complexity and Biosystems (CC&B) of the University of Milan, together with international collaborators from Radboud University Nijmagen and the Universities of Leipzig and Dresden, showed that in breast cancer the switch between single and collective cell migration can be controlled by a series of physical and biochemical factors including the stiffness of the extracellular matrix and the stability of cell-cell junctions.
To identify the critical factors contributing to breast cancer dissemination, the authors of the paper combined experiments in vitro, in 3D spheroids, and in vivo, in mice, with quantitative image analysis and computational models. The main result is that the dissemination of tumor cells is crucially dependent by E-cadherin which plays a fundamental role as adhesion molecule. However, changing the stiffness of the microenvironment (e.g. the density of the collagen matrix surrounding the cells) the authors are also able to induce a switch in the mode of cell migration. These intriguing results are also commented by the authors in Nature Reviews Physics.
“Being able to identify the control parameters of breast cancer dissemination is of crucial importance in order to fight metastasis, which is the main causes of death in cancer patients” says Caterina La Porta professor of general pathology at the Department of Environmental Science and Policy and CC&B of the University of Milan. “It is remarkable that concept and ideas routinely used in physics to describe phase transformation in materials find such a direct application in the behavior of cancer cells”, concludes Stefano Zapperi professor of theoretical physics of matter at the department of physics and at CC&B of the University of Milan.
References:
O. Ilina et al. Nature Cell Biology 2020 doi: 10.1038/s41556-020-0552-6
https://www.nature.com/articles/s41556-020-0552-6
C. A.M. La Porta and Stefano Zapperi, Nature Reviews Physics 2020 doi:10.1038/s42254-020-0213-5
https://www.nature.com/articles/s42254-020-0213-5