(447b) Breaking Away from the Pack: Lateral Compression Induces Single Cell Dissociation from Collectively Migrating Cancer Cells

Cell migration can broadly be characterized into two categories comprising of single cell motility and collectively migrating groups of cells. Single cell migration has been investigated extensively in a wide variety of systems, but there is much less known about the more efficient mode of collective migration. This mode of cell migration is prevalent within wound healing, developmental morphogenesis, and cancer. Within the context of cancer, collective migration plays a prominent role within the metastatic cascade, more specifically, tumor dissemination. Within tumor dissemination, single cells and cell clusters dissociate from the bulk primary tumor and migrate throughout the host to distant metastatic sites to form secondary metastasis. Our group has devised a novel in-vitro system using photolithography to fabricate PDMS microchannels of varying dimensions to study this phenomenon. Remarkably, we have observed that when A431 squamous cell carcinoma cells are subjected to increasing degrees of lateral compression in narrower microchannels, single cells tend to dissociate more from the bulk monolayer. We hypothesized that this can be due to a decrease in E-cadherin expression as the cells migrate through confined spaces. We also hypothesized that a variety of physical cues exerted by confining microchannels could be causing an increase in E-cadherin disengagement which could be responsible for the cell dissociation that was observed. To support this, A431 cells transfected with E-cadherin -GFP were utilized in a similar fashion to assess the role of E-cadherin in our system. Interestingly, the E-cadherin GFP overexpressing cells dissociated from the bulk population at markedly lower frequency than the wild type cells revealing a key role for E-cadherin in this process. We are currently exploring the roles of cell intrinsic forces including cell tension and traction forces, actomyosin contractility as well as the role of softer substrates (12-50 kPa) in regulating the expression and/or function of E-cadherin through confining spaces.