Impact of ECM Properties on Cell Migration and Metastasis

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The influence of cell-matrix interactions has broad application for tissue engineering, wound healing, and cancer biology. However, understanding these processes requires models that allow us to analyze pathways in a highly dynamic system while decoupling the various environmental cues.

By generating highly controlled and tunable biomaterials, our lab established the role of matrix physical and mechanical properties on the 3D cancer cell and T cell migration. Specifically, we have shown that collagen fiber density and stress relaxation modulate the ability of cancer cells to migrate and metastasize via the TGFb-SMAD2 axis (1,2). We further generated devices to align collagen fibers, thus modeling the physiological tumor microenvironment. We found that CD8+ T cells migrate persistently along aligned collagen fibers through myosin light chain kinase (3).

Using these models, we can dissect the mechanism by which mechanical and chemical properties of the microenvironment jointly modulate cell motility and metastasis, providing the basis for future fundamental studies into relevant therapeutic targets.

  1. Lewis DM, et al. Collagen Fiber Architecture Regulates Hypoxic Sarcoma Cell Migration. ACS Biomater. Sci. Eng. 2018; DOI:10.1021/acsbiomaterials.7b00056
  2. Lewis DM, et al. A feedback loop between hypoxia and matrix stress relaxation increases oxygen-axis migration and metastasis in sarcoma. Cancer Res. 2019; 79:1981-1995.
  3. Pruitt HC, et al. Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes. Matrix Biol. 2019; S0945-053X(18)30458-X