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Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment

Lachowski, Dariusz; orcid: 0000-0003-1194-8019; email: d.lachowski15@imperial.ac.uk
Matellan, Carlos; orcid: 0000-0002-3589-6252; email: c.matellan16@imperial.ac.uk
Cortes, Ernesto; orcid: 0000-0001-6106-1323; email: j.e.corteslopez@imperial.ac.uk
Saiani, Alberto; email: a.saiani@manchester.ac.uk
Miller, Aline F.; email: a.miller@manchesterbiogel.com
del Río Hernández, Armando E.; orcid: 0000-0001-5062-8910; email: a.del-rio-hernandez@imperial.ac.uk
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2021-06-30
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Abstract
The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).
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Cancers, volume 13, issue 13, page e3286
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MDPI
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From MDPI via Jisc Publications Router
History: accepted 2021-06-25, pub-electronic 2021-06-30
Publication status: Published
Funder: Innovate UKRI Research Knowledge Transfer Partnership; Grant(s): KTP: Self-assembling peptide matrices as a platform for cell biology studies and drug delivery
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