Unjamming and collective migration in MCF10A breast cancer cell lines

Abstract

Each cell comprising an intact, healthy, confluent epithelial layer ordinarily remains sedentary, firmly adherent to and caged by its neighbors, and thus defines an elemental constituent of a solidlike cellular collective [1,2]. After malignant transformation, however, the cellular collective can become fluid-like and migratory, as evidenced by collective motions that arise in characteristic swirls, strands, ducts, sheets, or clusters [3,4]. To transition from a solid-like to a fluid-like phase and thereafter to migrate collectively, it has been recently argued that cells comprising the disordered but confluent epithelial collective can undergo changes of cell shape so as to overcome geometric constraints attributable to the newly discovered phenomenon of cell jamming and the associated unjamming transition (UJT) [1,2,[5][6][7][8][9]. Relevance of the jamming concept to carcinoma cells lines of graded degrees of invasive potential has never been investigated, however. Using classical in vitro cultures of six breast cancer model systems, here we investigate structural and dynamical signatures of cell jamming, and the relationship between them [1,2,10,11]. In order of roughly increasing invasive potential as previously reported, model systems examined included MCF10A, MCF10A.Vector; MCF10A. MCF10.ErbB2, MCF10AT;. Migratory speed depended on the particular cell line. Unsurprisingly, for example, the

Distinct Roles of Tumor-Associated Mutations in Collective Cell Migration

“…2h, which shows higher spatial coordination in the MCF10A cell line. Our finding that the MDA-MB-231 cells exhibit a less collective migration phenotype than the MCF10A cells is in agreement with previous studies which have found disordered collective behavior in cancer cell types 16,28 . Next we investigated the collective behavior of a genetically defined cancer model system which has been previously characterized in vivo for both primary tumorigenesis and metastatic efficiency 23,24 .…”

“…Plasticity in collective behavior is also seen through the framework of an unjamming transition, which can allow epithelial monolayers to flow collectively without necessitating the activation of EMTtranscription factors or expression of mesenchymal markers 15 . Signatures of unjamming have been observed in both non-tumorigenic MCF10A cells and in MCF10A-based models of breast cancer 16,17 . Unjamming also allows mesenchymal tumor cells to adapt to their surroundings and migrate collectively 18 .…”

Cell jamming, stratification and p63 expression in cultivated human corneal epithelial cell sheets

“…Based on these observations, we suggest a relationship between stratification of an expanding cultivated LEC sheet and cell jamming. Interestingly, we speculate that the transition from jamming to unjamming that was observed in specimens 1 and 2 after around 8 days in culture might relate to morphological changes in cells, as well as to overcrowding due to proliferation as has been suggested elsewhere 26,27,[33][34][35][36][37] . To further understand jamming-unjamming phenomena, a kinetic interpretation focusing on the sheet formation and degradation rates due to turnover is probably warranted.…”

Epithelial layer unjamming shifts energy metabolism toward glycolysis

“…The epithelial layer is ordinarily non-migratory, jammed and quiescent but all the time retains the capacity to unjam and, in doing so, transition to a migratory phase in response to the demand for tissue development, growth, remodeling or wound repair 19 , 29 , 49 . It has been suggested that these salutary unjamming behaviors can sometimes become hijacked in disease, however, and thereby initiate unwelcomed cellular migration and tissue remodeling as in the cases of tumor invasion or asthmatic remodeling of the airway wall 24 , 50 – 53 . In the advancing confluent MDCKII monolayer, here we have integrated multiple modes of metabolic imaging in order to characterize with single cell precision the metabolic state simultaneously with metrics of cell morphology, migration, and mechanics.…”