Assistant Professor Department of Surgery, Division of General Surgery, Indiana University School of Medicine Indiana University Melvin and Bren Simon Cancer Center IU Center for Computationa
Invading cancer cells leave the tumor to form distant metastases and are ultimately responsible for 90% of deaths in cancer. Reducing the ability of cancer cells to invade and metastasize could extend the life of cancer patients. However, our current understanding of the conditions that trigger and guide the invasion of cancer cells is insufficient and our abilities to interfere with these processes are limited. By using novel microfluidic tools, we uncovered an unexpected ability of cancer cells to navigate and exit microscopic mazes along the shortest path. To explain this behavior, we propose a novel mechanism that guides cancer cell migration. This mechanism depends on the generation of spatial chemical gradients by the cancer cell themselves, through the competition between epidermal growth factor (EGF) uptake by the cells and the restricted diffusion of EGF from surrounding microenvironment to the cells. Employing this strategy when placed in uniform but confined environments, cancer cells can self-generate spatial gradients of EGF, effectively mapping the environment, and guiding their own escape from the confinement. Better understanding of the cancer cell guidance strategy by self-generated gradients could lead to approaches for restricting the migration of malignant cells to delay local invasion and distant metastases. Learning objectives: - Identify the environment settings that trigger self-guided cell migration; - Recognize the conditions that favor cancer cell invasion; - Predict the patterns of cancer cell migration in various conditions of confinement; - Suggest interventions that may perturb the self-guidance of cancer cells.