Abstract A62: Unjamming and spreading of a cellular aggregate as a model of breast cancer migration

Abstract

Abstract Traditional understanding holds that metastasis begins as tumor cells undergo epithelial-to-mesenchymal transition (EMT) to migrate and escape. Recent studies suggest that EMT is not necessary for metastasis, however. Tumor cells may retain their epithelial phenotype to migrate collectively during metastasis. But if EMT is not the crucial permissive step, what is? Our group recently discovered cellular jamming; a process by which an epithelial layer is dormant, non-migratory, and solid-like, corresponding to the jammed state, but in other circumstances becomes active, migratory, and fluid-like, corresponding to the unjammed state. Therefore, based on this phenomenon, do breast cancer cells unjam before they can collectively migrate and metastasize? Spheroidal aggregates of MCF10A and MDA-MB-231 cells spreading on collagen-coated polyacrylamide gels, modeling normal and malignant breast epithelium, respectively, were used to investigate cell jamming, cell-matrix adhesion, and associated traction forces. Compared with MCF10A spheroids, MDA-MB-231 spheroids permeated more rapidly onto gels, generated largely localized traction forces, and dissociated to spread more rapidly outwards. These results suggest MDA-MB-231 cells are more susceptible to unjamming and collective migration. This work will provide a new framework by which to explain collective cellular behavior of normal and malignant breast epithelium. Citation Format: Karin Wang, Jeffrey J. Fredberg. Unjamming and spreading of a cellular aggregate as a model of breast cancer migration. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A62.