Abstract 5061: Evaluating the role of durotactic migration in the tumor microenvironment

Abstract

Abstract Durotaxis is a mechanism of directional migration in which cells respond to a stiffness gradient in their local microenvironment. While durotaxis has been characterized primarily in cells of mesenchymal origin, its role in cancer biology has not been clearly defined. At a cellular and molecular level, evidence suggests cancer cells sense and respond to the stiffening tumor microenvironment in a manner that promotes malignant and invasive characteristics. Given the gradual stiffening of tumors, it is interesting to speculate how durotaxis might contribute to cell flux to and from primary tumors and metastatic sites. We hypothesize that a durotactic mechanism may, in part, contribute to the dissemination of cancer cells into the stiffened microenvironment associated with primary tumors and also possibly with pre-metastatic sites. To directly characterize the impact of local stiffness on directional migration, cancer cells were cultured on a hydrogel possessing a stiffness gradient, then imaged by time-lapse microscopy and tracked using custom automated tracking software. Automated cell tracking allows for unbiased, accurate, and high-speed generation of large migratory datasets not feasible with conventional manual tracking and enables more robust analysis of cell populations. Preliminary data reveal that multiple cancer cell lines respond to a stiffness gradient with directed migration towards the stiffer part of the gel. The strength of the directional migratory response to stiffness gradients was found to depend on the magnitude of stiffness a cell encounters. By manipulating stiffness gradients to accurately reflect stiffness encountered by cancer subtypes, we will better understand if a durotactic mechanism has a global or cancer-specific impact on disease progression. Citation Format: Brian J. DuChez, Kenneth M. Yamada. Evaluating the role of durotactic migration in the tumor microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5061.