Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy

Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy

A better understanding of how microenvironmental factors regulate cancer dormancy is needed for development of new therapeutic strategies to control metastatic recurrence and disease progression. Modeling cancer dormancy using engineered, in vitro platforms is necessary for investigation under well-...

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Main Authors: Shantanu Pradhan, John H. Slater
Format: Article
Language:English
Published: Elsevier 2019-01-01
Series:MethodsX
Online Access:http://www.sciencedirect.com/science/article/pii/S2215016119303140
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spelling doaj-c88c84224b594b0399109741c8d89c342020-11-25T01:40:40ZengElsevierMethodsX2215-01612019-01-01627442766Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancyShantanu Pradhan0John H. Slater1Department of Biomedical Engineering, University of Delaware, Newark, DE, USADepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA; Department of Materials Science & Engineering, University of Delaware, Newark, DE, USA; Delaware Biotechnology Institute, Newark, DE, USA; Corresponding author at: Department of Biomedical Engineering, University of Delaware, USA.A better understanding of how microenvironmental factors regulate cancer dormancy is needed for development of new therapeutic strategies to control metastatic recurrence and disease progression. Modeling cancer dormancy using engineered, in vitro platforms is necessary for investigation under well-defined and well-controlled microenvironments. We present methods and protocols to fabricate, characterize, and implement engineered hydrogels with well-defined biochemical and physical properties for control over breast cancer cell phenotype in three-dimensional (3D) culture. Changes in hydrogel adhesivity, crosslink density, and degradability induce a range of phenotypic behaviors in breast cancer cells including: (1) high growth, (2) moderate growth, (3) single cell, restricted survival dormancy, and (4) balanced dormancy. We describe a method of classifying hydrogel formulations that support each of these phenotypic states. We also describe a method to phenotypically switch cancer cells from single cell dormancy to high growth by dynamically modulating ligand density, thereby recapitulating reactivation and metastatic recurrence. Protocol name: Methods to characterize hydrogel properties, Quantification of cellular metrics, Phenotypic classification of cancer cell states, Keywords: Biomaterials, Tissue engineering, Hydrogel, PEG, Cancer, Dormancy, Metastasis, Relapse, Microenvironmenthttp://www.sciencedirect.com/science/article/pii/S2215016119303140
collection DOAJ
language English
format Article
sources DOAJ
author Shantanu Pradhan
John H. Slater
spellingShingle Shantanu Pradhan
John H. Slater
Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
MethodsX
author_facet Shantanu Pradhan
John H. Slater
author_sort Shantanu Pradhan
title Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
title_short Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
title_full Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
title_fullStr Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
title_full_unstemmed Fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
title_sort fabrication, characterization, and implementation of engineered hydrogels for controlling breast cancer cell phenotype and dormancy
publisher Elsevier
series MethodsX
issn 2215-0161
publishDate 2019-01-01
description A better understanding of how microenvironmental factors regulate cancer dormancy is needed for development of new therapeutic strategies to control metastatic recurrence and disease progression. Modeling cancer dormancy using engineered, in vitro platforms is necessary for investigation under well-defined and well-controlled microenvironments. We present methods and protocols to fabricate, characterize, and implement engineered hydrogels with well-defined biochemical and physical properties for control over breast cancer cell phenotype in three-dimensional (3D) culture. Changes in hydrogel adhesivity, crosslink density, and degradability induce a range of phenotypic behaviors in breast cancer cells including: (1) high growth, (2) moderate growth, (3) single cell, restricted survival dormancy, and (4) balanced dormancy. We describe a method of classifying hydrogel formulations that support each of these phenotypic states. We also describe a method to phenotypically switch cancer cells from single cell dormancy to high growth by dynamically modulating ligand density, thereby recapitulating reactivation and metastatic recurrence. Protocol name: Methods to characterize hydrogel properties, Quantification of cellular metrics, Phenotypic classification of cancer cell states, Keywords: Biomaterials, Tissue engineering, Hydrogel, PEG, Cancer, Dormancy, Metastasis, Relapse, Microenvironment
url http://www.sciencedirect.com/science/article/pii/S2215016119303140
work_keys_str_mv AT shantanupradhan fabricationcharacterizationandimplementationofengineeredhydrogelsforcontrollingbreastcancercellphenotypeanddormancy
AT johnhslater fabricationcharacterizationandimplementationofengineeredhydrogelsforcontrollingbreastcancercellphenotypeanddormancy
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