Taubenberger A, Girardo S, Traeber N, Fischer-Friedrich E, Kraeter M, Wagner K, Kurth T, Richter I, Haller B, Binner M, Hahn D, Freudenberg U, Werner C, Guck J (2019)
Publication Type: Journal article
Publication year: 2019
Book Volume: 3
Article Number: 1900128
Journal Issue: 9
The mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using 2D substrates, much less is known about it in a physiologically more relevant 3D context. Here it is demonstrated that breast cancer tumor spheroids, growing in 3D polyethylene glycol-heparin hydrogels, are sensitive to their environment stiffness. During tumor spheroid growth, compressive stresses of up to 2 kPa build up, as quantitated using elastic polymer beads as stress sensors. Atomic force microscopy reveals that tumor spheroid stiffness increases with hydrogel stiffness. Also, constituent cell stiffness increases in a Rho associated kinase (ROCK)- and F-actin-dependent manner. Increased hydrogel stiffness correlated with attenuated tumor spheroid growth, a higher proportion of cells in G0/G1 phase, and elevated levels of the cyclin-dependent kinase inhibitor p21. Drug-mediated ROCK inhibition not only reverses cell stiffening upon culture in stiff hydrogels but also increases tumor spheroid growth. Taken together, a mechanism by which the growth of a tumor spheroid can be regulated via cytoskeleton rearrangements in response to its mechanoenvironment is revealed here. Thus, the findings contribute to a better understanding of how cancer cells react to compressive stress when growing under confinement in stiff environments.
APA:
Taubenberger, A., Girardo, S., Traeber, N., Fischer-Friedrich, E., Kraeter, M., Wagner, K.,... Guck, J. (2019). 3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK. Advanced Biosystems, 3(9). https://doi.org/10.1002/adbi.201900128
MLA:
Taubenberger, Anna, et al. "3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK." Advanced Biosystems 3.9 (2019).
BibTeX: Download