Affiliation:
1. 3B's Research Group I3Bs – Research Institute on Biomaterials Biodegradables and Biomimetics of University of Minho Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine AvePark, Zona Industrial da Gandra, Barco Guimarães 4805‐017 Portugal
2. ICVS/3B's – PT Government Associated Laboratory Braga/Guimarães 4805‐017 Portugal
Abstract
AbstractBreast cancer is still the leading cause of women's death due to relapse and metastasis. In vitro tumor models are considered reliable tools for drug screening and understanding cancer‐driving mechanisms due to the possibility of mimicking tumor heterogeneity. Herein, a 3D breast cancer model (3D‐BCM) is developed based on enzymatically‐crosslinked silk fibroin (eSF) hydrogels. Human MCF7 breast cancer cells are encapsulated into eSF hydrogels, with and without human mammary fibroblasts. The spontaneously occurring conformational change from random coil to β‐sheet is correlated with increased eSF hydrogels’ stiffness over time. Moreover, mechanical properties analysis confirms that the cells can modify the stiffness of the hydrogels, mimicking the microenvironment stiffening occurring in vivo. Fibroblasts support cancer cells growth and assembly in the eSF hydrogels up to 14 days of culture. Co‐cultured 3D‐BCM exhibits an upregulated expression of genes related to extracellular matrix remodeling and fibroblast activation. The 3D‐BCM is subjected to doxorubicin and paclitaxel treatments, showing differential drug response. Overall, these results suggest that the co‐culture of breast cancer cells and fibroblasts in eSF hydrogels allow the development of a mimetic in vitro platform to study cancer progression. This opens up new research avenues to investigate novel molecular targets for anti‐cancer therapy.
Funder
Fundação para a Ciência e a Tecnologia
Horizon 2020 Framework Programme
Subject
General Biochemistry, Genetics and Molecular Biology,Biomedical Engineering,Biomaterials
Cited by
1 articles.
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1. Trends in silk biomaterials;Silk-Based Biomaterials for Tissue Engineering, Regenerative and Precision Medicine;2024