Abstract A37: ‘Touch-and-go' behavior of cancer cells in spatially-confined, fiber-like microenvironments

Abstract

In a crowded, fibrillar tumor microenvironment (TMEN), invading cancer cells encounter and interact with many other cells and cell types. Whether cancer cells stop migrating or reverse direction at every encounter with another cell, or circumnavigate and slide around the encounter, will affect the efficiency of the invasion process. We find that breast cancer cells migrating along fiber-like micropatterns (FLMs) respond differently to cell-cell encounters than what is expected based on the classically-established phenotype of contact-inhibition of locomotion (CIL). Cancer cells are remarkable efficient at sliding around other cancer cells, even along FLMs much narrower than their own cell body. In contrast, non-transformed breast epithelial cells reverse direction upon encountering other normal cells. Differences in cell size fail to predict these outcomes. Interestingly, the participation of normal cells in invasive sliding behavior increases when interacting with a cancer cell rather than another a normal cell. This induction of cancer-like behavior in normal cells suggests that heterotypic interactions between disparate cell types in the TMEN may produce synergistic, disease-promoting collective behaviors. Furthermore, using a series of individual and combinatorial genetic perturbations, we show that genetic factors (ErbB2, E-cadherin, PARD3, TGFbeta) quantitatively shift the ability of normal cells to slide. Specifically, successive genetic perturbations enable normal cells to slide on progressively narrower FLMs. These results suggest that as fibers align and mature during cancer progression, coincident genetic perturbations enable cells to take advantage of the widening fibrillar tracks to execute slides and achieve more efficient dispersion in a crowded microenvironment. Citation Format: Daniel Milano, Senthil Muthuswamy, Anand Asthagiri. ‘Touch-and-go' behavior of cancer cells in spatially-confined, fiber-like microenvironments. [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 A37.