Probing the role of tissue mechanics in cancer cell dormancy

In the case of breast cancer, patients showing one sub-type may appear disease free for several years before relapsing with brain metastasis. Improved clinical control requires a better understanding of cancer dormancy. Using in vitro models, proteins critical for mechanotransduction regulate emergence from the dormant state. Therefore, we reasoned that the physical microenvironment may regulate reawakening. Here, we mapped the intracellular and extracellular cell and matrix mechanics with near simultaneity as a function of ECM stiffness for PDMS gels and brain mimetic HA gels using optical tweezers to perform active microrheology. The intracellular stiffness of dormant cells embedded in gels was stiffer than the aggressive cells. Comparable measurements to thin sections of excised tumors grown subcutaeneously showed a similar trend. A differential local remodeling of matrix was measured between clones. Taken together, our results suggest that dormant and aggressive cells may respond differently to the brain microenvironment, exhibiting distinct morphology, mechanical properties and ECM remodeling, which bear on their ability to colonize the brain.