Effects of Migrating Cell-Induced Matrix Reorganization on 3D Cancer Cell Migration
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The migration of cells is fundamental to a number of physiological/pathological processes, ranging from embryonic development, tissue regeneration to cancer metastasis. Current research on cell migration is largely based on simplified in vitro models that assume a homogeneous microenvironment and overlook the modification of extracellular matrix (ECM) by the cells. To address this shortcoming, we developed a nested three-dimensional (3D) collagen hydrogel model mimicking the connective tissue confronted by highly malignant breast cancer cells, MDA-MB-231. Strikingly, our findings revealed two distinct cell migration patterns: a rapid and directionally persistent collective migration of the leader cells and a more randomized migration in the regions that have previously been significantly modified by cells. The cell-induced modifications, which typically include clustering and alignment of fibers, effectively segmented the matrix into smaller sub-regions. Our results suggest that in an elastic 3D matrix, the presence of adjacent cells that have modified the matrix may in fact become physical hurdle to a migrating cell. Furthermore, our study emphasizes the need for a micromechanical understanding in the context of cancer invasion that allows for cell-induced modification of ECM and a heterogeneous cell migration.
KeywordsCancer invasion 3D extracellular matrix Collective cell migration Matrix remodeling Cell contraction
Supports provided by the Global Enterprise for Micro-Mechanics and Molecular Medicine (GEM4) and the NUS Graduate School for Integrative Sciences and Engineering are gratefully acknowledged.
Conflict of interest
W. Sun, N. A. Kurniawan, A. P. Kumar, R. Rajagopalan, and C. T. Lim declare that they have no conflicts of interest.
No human or animal studies were carried out by the authors for this article.
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