TY - JOUR
T1 - The Effect of Geometry and TGF-β Signaling on Tumor Cell Migration from Free-Standing Microtissues
AU - Xie, Jing
AU - Hu, Xinyu
AU - Chen, Lina
AU - Piruska, Aigars
AU - Zheng, Zijian
AU - Bao, Min
AU - Huck, Wilhelm T.S.
N1 - Funding Information:
The authors thank Manon Bertrand for the tests of different cell lines; the authors also thank Baoxiu Wang for the assistance of alginate gels optimization. The authors are grateful to the Department of General Instruments of Radboud University for providing Leica Sp8 confocal microscopy services. The authors would like to acknowledge Prof. Joachim Spatz for the support of TGF-β regulation experiments by providing TGF-β, MDA-MB-231 cells, and antibodies for vimentin, Lamin A/C and YAP/TAZ staining, which were performed in the department of cellular biophysics, Max Planck Institute for medical research, Germany. J.X. also acknowledges financial support from the China Scholarship Council and the Max Planck Institute.
Funding Information:
The authors thank Manon Bertrand for the tests of different cell lines; the authors also thank Baoxiu Wang for the assistance of alginate gels optimization. The authors are grateful to the Department of General Instruments of Radboud University for providing Leica Sp8 confocal microscopy services. The authors would like to acknowledge Prof. Joachim Spatz for the support of TGF‐ regulation experiments by providing TGF‐, MDA‐MB‐231 cells, and antibodies for vimentin, Lamin A/C and YAP/TAZ staining, which were performed in the department of cellular biophysics, Max Planck Institute for medical research, Germany. J.X. also acknowledges financial support from the China Scholarship Council and the Max Planck Institute. β β
Publisher Copyright:
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2022/6
Y1 - 2022/6
N2 - Recapitulation of 3D multicellular tissues in vitro is of great interest to the field of tumor biology to study the integrated effect of local biochemical and biophysical signals on tumor cell migration and invasion. However, most microengineered tissues and spheroids are unable to recapitulate in vitro the complexities of 3D geometries found in vivo. Here, lithographically defined degradable alginate microniches are presented to produce free-standing tumor microtissues, with precisely controlled geometry, high viability, and allowing for high cell proliferation. The role of microtissue geometry and TGF-β signaling in tumor cell migration is further investigated. TGF-β is found to induce the expression of p-myosin II, vimentin, and YAP/TAZ nuclear localization at the periphery of the microtissue, where enhanced nuclear stiffness and orientation are also observed. Upon embedding in a collagen matrix, microtissues treated with TGF-β maintain their geometric integrity, possibly due to the higher cell tension observed around the periphery. In contrast, cells in microtissues not treated with TGF-β are highly mobile and invade the surrounding matrix rapidly, with the initial migration strongly dependent on the local geometry. The microtissues presented here are promising model systems for studying the influence of biophysical properties and soluble factors on tumor cell migration.
AB - Recapitulation of 3D multicellular tissues in vitro is of great interest to the field of tumor biology to study the integrated effect of local biochemical and biophysical signals on tumor cell migration and invasion. However, most microengineered tissues and spheroids are unable to recapitulate in vitro the complexities of 3D geometries found in vivo. Here, lithographically defined degradable alginate microniches are presented to produce free-standing tumor microtissues, with precisely controlled geometry, high viability, and allowing for high cell proliferation. The role of microtissue geometry and TGF-β signaling in tumor cell migration is further investigated. TGF-β is found to induce the expression of p-myosin II, vimentin, and YAP/TAZ nuclear localization at the periphery of the microtissue, where enhanced nuclear stiffness and orientation are also observed. Upon embedding in a collagen matrix, microtissues treated with TGF-β maintain their geometric integrity, possibly due to the higher cell tension observed around the periphery. In contrast, cells in microtissues not treated with TGF-β are highly mobile and invade the surrounding matrix rapidly, with the initial migration strongly dependent on the local geometry. The microtissues presented here are promising model systems for studying the influence of biophysical properties and soluble factors on tumor cell migration.
KW - cell migration
KW - free-standing microtissues
KW - TGF-β signaling
KW - tissue geometry
UR - http://www.scopus.com/inward/record.url?scp=85125227865&partnerID=8YFLogxK
U2 - 10.1002/adhm.202102696
DO - 10.1002/adhm.202102696
M3 - Journal article
C2 - 35182463
AN - SCOPUS:85125227865
SN - 2192-2640
VL - 11
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 12
M1 - 2102696
ER -