Heparin-based hydrogel scaffolding alters the transcriptomic profile and increases the chemoresistance of MDA-MB-231 triple-negative breast cancer cells

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dc.contributor.authorMenon, Nidhien
dc.contributor.authorDang, Ha X.en
dc.contributor.authorDatla, Udaya Sreeen
dc.contributor.authorMoarefian, Maryamen
dc.contributor.authorLawrence, Christopher B.en
dc.contributor.authorMaher, Christopher A.en
dc.contributor.authorJones, Caroline N.en
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentMechanical Engineeringen
dc.date.accessioned2020-12-23T18:08:33Zen
dc.date.available2020-12-23T18:08:33Zen
dc.date.issued2020-05-21en
dc.description.abstractThe tumor microenvironment plays a critical role in the proliferation and chemoresistance of cancer cells. Growth factors (GFs) are known to interact with the extracellular matrix (ECM) via heparin binding sites, and these associations influence cell behavior. In the present study, we demonstrate the ability to define signals presented by the scaffold by pre-mixing growth factors, such as epidermal growth factor, into the heparin-based (HP-B) hydrogel prior to gelation. In the 3D biomimetic microenvironment, breast cancer cells formed spheroids within 24 hours of initial seeding. Despite higher number of proliferating cells in 2D cultures, 3D spheroids exhibited a higher degree of chemoresistance after 72 hours. Further, our RNA sequencing results highlighted the phenotypic changes influenced by solid-phase GF presentation. Wnt/beta-catenin and TGF-beta signaling were upregulated in the cells grown in the hydrogel, while apoptosis, IL2-STAT5 and PI3K-AKT-mTOR signaling were downregulated. With emerging technologies for precision medicine in cancer, this nature of fine-tuning the microenvironment is paramount for cultivation and downstream characterization of primary cancer cells and rare circulating tumor cells (CTCs), and effective screening of chemotherapeutic agents.en
dc.description.notesWe would like to thank Carla Finkielstein for her thoughtful discussions on experimental design and RNA seq data analysis. Research reported in this publication was supported by The National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133610.en
dc.description.sponsorshipNational Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R35GM133610]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1039/c9bm01481ken
dc.identifier.eissn2047-4849en
dc.identifier.issn2047-4830en
dc.identifier.issue10en
dc.identifier.pmid32091043en
dc.identifier.urihttp://hdl.handle.net/10919/101619en
dc.identifier.volume8en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleHeparin-based hydrogel scaffolding alters the transcriptomic profile and increases the chemoresistance of MDA-MB-231 triple-negative breast cancer cellsen
dc.title.serialBiomaterials Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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