3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity

Autor: Theo Desigaux, Leo Comperat, Nathalie Dusserre, Marie-Laure Stachowicz, Malou Lea, Jean-William Dupuy, Anthony Vial, Michael Molinari, Jean-Christophe Fricain, François Paris, Hugo Oliveira
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Bioactive Materials, Vol 42, Iss , Pp 316-327 (2024)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2024.08.037
Popis: Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.
Databáze: Directory of Open Access Journals