Differential stiffness between brain vasculature and parenchyma promotes metastatic infiltration through vessel co-option.

Autor: Uroz M; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Stoddard AE; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA.; Harvard-MIT Program in Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA., Sutherland BP; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Courbot O; Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, London, UK.; Department of Physics, King's College London, London, UK., Oria R; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA., Li L; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA.; Department of Chemical Engineering, University of New Hampshire, Durham, NH, USA., Ravasio CR; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Ngo MT; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Yang J; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Tefft JB; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Eyckmans J; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.; Biological Design Center, Boston University, Boston, MA, USA., Han X; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Elosegui-Artola A; Cell and Tissue Mechanobiology Laboratory, The Francis Crick Institute, London, UK.; Department of Physics, King's College London, London, UK., Weaver VM; Department of Surgery, University of California, San Francisco, CA, USA.; Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA, USA.; UCSF Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.; Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA., Chen CS; Department of Biomedical Engineering, Boston University, Boston, MA, USA. chencs@bu.edu.; The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. chencs@bu.edu.; Biological Design Center, Boston University, Boston, MA, USA. chencs@bu.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Oct 24. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1038/s41556-024-01532-6
Abstrakt: In brain metastasis, cancer cells remain in close contact with the existing vasculature and can use vessels as migratory paths-a process known as vessel co-option. However, the mechanisms regulating this form of migration are poorly understood. Here we use ex vivo brain slices and an organotypic in vitro model for vessel co-option to show that cancer cell invasion along brain vasculature is driven by the difference in stiffness between vessels and the brain parenchyma. Imaging analysis indicated that cells move along the basal surface of vessels by adhering to the basement membrane extracellular matrix. We further show that vessel co-option is enhanced by both the stiffness of brain vasculature, which reinforces focal adhesions through a talin-dependent mechanism, and the softness of the surrounding environment that permits cellular movement. Our work reveals a mechanosensing mechanism that guides cell migration in response to the tissue's intrinsic mechanical heterogeneity, with implications in cancer invasion and metastasis.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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