Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.

Autor: Zhang S; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Grifno G; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Passaro R; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Regan K; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Zheng S; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Hadzipasic M; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA., Banerji R; Department of Biomedical Engineering, Boston University, Boston, MA, USA., O'Connor L; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Chu V; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Kim SY; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Yang J; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Shi L; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Karrobi K; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Roblyer D; Department of Biomedical Engineering, Boston University, Boston, MA, USA., Grinstaff MW; Department of Biomedical Engineering, Boston University, Boston, MA, USA.; Department of Chemistry, Boston University, Boston, MA, USA., Nia HT; Department of Biomedical Engineering, Boston University, Boston, MA, USA. htnia@bu.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Nov; Vol. 7 (11), pp. 1473-1492. Date of Electronic Publication: 2023 Aug 28.
DOI: 10.1038/s41551-023-01080-8
Abstrakt: In cancer, solid stresses impede the delivery of therapeutics to tumours and the trafficking and tumour infiltration of immune cells. Understanding such consequences and the origin of solid stresses requires their probing in vivo at the cellular scale. Here we report a method for performing volumetric and longitudinal measurements of solid stresses in vivo, and findings from its applicability to tumours. We used multimodal intravital microscopy of fluorescently labelled polyacrylamide beads injected in breast tumours in mice as well as mathematical modelling to compare solid stresses at the single-cell and tissue scales, in primary and metastatic tumours, in vitro and in mice, and in live mice and post-mortem tissue. We found that solid-stress transmission is scale dependent, with tumour cells experiencing lower stresses than their embedding tissue, and that tumour cells in lung metastases experience substantially higher solid stresses than those in the primary tumours. The dependence of solid stresses on length scale and the microenvironment may inform the development of therapeutics that sensitize cancer cells to such mechanical forces.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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