Epithelial layer jamming in collective cancer cell migration

Breast cancer is representative of the wider class of cancers of epithelial origin (carcinomas) that account for the vast majority of cancers and cancer deaths. If cancer cells did not migrate and instead just stayed put, then cancer in most instances would be a more manageable disease. But cancer cells do migrate, and that migration accounts for much of cancer’s morbidity and mortality. Unfortunately, we understand little about how, why, and when this aberrant cellular migration plays out. Cancer cells tend to migrate not as individual units but rather as a cellular collective in multicellular strings, ducts, strands and clusters.

It is proposed that a controlling factor in the collective cellular migration is a newly discovered phenomenon called "cell jamming." Do epithelial cells in some circumstances behave in one way (jammed, solid-like and aggregated with little possibility of mutual cell rearrangement, escape or invasion), while in other circumstances they behave in another (unjammed, fluid-like, disaggregated and invasive)? In collaboration with Dr. Jeffrey Fredberg at Harvard School of Public Health and Dr. Muhammad Zaman at Boston University, we will address this question in selected breast cancer cell lines, in a variety of extracellular environments that mimic native environments, and across graded stages of the epithelial-to-mesenchymal transition. Data derived from a comprehensive suite of novel experimental probes — cellular motions, traction stresses, intercellular stresses and cellular shapes — will be critically examined through the lens of a novel quantitative theory of cell jamming.

Faculty contact: Zi Chen