When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-Like Microcapsules

Antonelli Y, Krüger R, Bühler A, Monavari M, Fuentes Chandia MA, Colombo F, Palmisano R, Boßerhoff AK, Kappelmann-Fenzl M, Schödel J, Boccaccini AR, Selhuber-Unkel C, Letort G, Leal-Egaña A (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Advanced Functional Materials Wiley-VCH Verlag

Article Number: 2311139

DOI: 10.1002/adfm.202311139

Abstract

Biofabrication techniques enable the performance of bioinspired three-dimensional (3D) matrices resembling primary tumors. To validate their reliability, embedded cells may express complex biophysical responses. Among others, the emergence of tumor heterogeneity and the generation of Polyploid Giant Cancer Cells (PGCC), as a result of the mechanical stress, are two of the most challenging hallmarks to resemble in vitro. Here, these phenomena are studied in cells cultured on two-dimensional (2D) flasks, in 3D spheroids, or immobilized within 3D polymer-based tumor-like microcapsules. These results show that cells cultured in 3D microcapsules exhibited an enhanced biomechanical heterogeneity, a higher number of PGCC, and an increased exertion of cell-matrix attachment forces with respect to the other two experimental conditions. Additionally, cells isolated from tumor-like microcapsules redistribute and align the cytoplasmatic protein Caveolin-1, and upregulate markers involved in cell proliferation (i.e., Ki67), metastasis (i.e., TGF-β1, TGF-β-R2), and epithelial to mesenchymal transition, to name a few. These hallmarks are barely described in the past as a result of the confinement and mechanical stress. Thus, in this work it is demonstrated that both the mechanical stress and confinement are required to stimulate cell polyploidy and biomechanical heterogeneity, which can be easily addressed by immobilizing breast cancer cells in tumor-like microcapsules.

Authors with CRIS profile

René Krüger Department of Medicine 4 – Nephrology and Hypertension Adrian Bühler Lehrstuhl für Medizinische Biotechnologie Mahshid Monavari Lehrstuhl für Werkstoffwissenschaften (Biomaterialien) Miguel Angel Fuentes Chandia Lehrstuhl für Werkstoffwissenschaften (Biomaterialien) Ralf Palmisano FAU Optical Imaging Competence Center (FAU OICE) Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Melanie Kappelmann-Fenzl Lehrstuhl für Biochemie und Molekulare Medizin Johannes Schödel Department of Medicine 4 – Nephrology and Hypertension Aldo Boccaccini Lehrstuhl für Werkstoffwissenschaften (Biomaterialien)

Additional Organisation(s)

FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

Involved external institutions

Institut Pasteur FR France (FR) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Antonelli, Y., Krüger, R., Bühler, A., Monavari, M., Fuentes Chandia, M.A., Colombo, F.,... Leal-Egaña, A. (2024). When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-Like Microcapsules. Advanced Functional Materials. https://doi.org/10.1002/adfm.202311139

MLA:

Antonelli, Yasmin, et al. "When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-Like Microcapsules." Advanced Functional Materials (2024).

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