Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance
Summary: Tumors comprised a tightly surrounded tumor microenvironment, made up of non-cellular extracellular matrix (ECM) and stromal cells. Although treatment response is often attributed to tumor heterogeneity, progression and malignancy are profoundly influenced by tumor cell interactions with th...
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220310488 |
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doaj-40fdf32883604c73aa7c90b2703b96b92020-12-19T05:10:09ZengElsevieriScience2589-00422020-12-012312101851Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and ChemoresistanceAnthony Dominijanni0Mahesh Devarasetty1Shay Soker2Wake Forest University School of Medicine, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, USAWake Forest University School of Medicine, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, USAWake Forest University School of Medicine, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC 27101, USA; Corresponding authorSummary: Tumors comprised a tightly surrounded tumor microenvironment, made up of non-cellular extracellular matrix (ECM) and stromal cells. Although treatment response is often attributed to tumor heterogeneity, progression and malignancy are profoundly influenced by tumor cell interactions with the surrounding ECM. Here, we used a tumor organoid model, consisting of hepatic stellate cells (HSCs) embedded in collagen type 1 (Col1) and colorectal cancer cell (HCT-116) spheroids, to determine the relationship between the ECM architecture, cancer cell malignancy, and chemoresistance. Exogenous transforming growth factor beta (TGF-β) used to activate the HSCs increased the remodeling and bundling of Col1 in the ECM around the cancer spheroid. A dense ECM architecture inhibited tumor cell growth, reversed their mesenchymal phenotype, preserved stem cell population, and reduced chemotherapy response. Overall, our results demonstrate that controlled biofabrication and manipulation of the ECM in tumor organoids results enables studying tumor cell-ECM interactions and better understand tumor cell response to chemotherapies.http://www.sciencedirect.com/science/article/pii/S2589004220310488Biological SciencesCancerBioengineering |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anthony Dominijanni Mahesh Devarasetty Shay Soker |
spellingShingle |
Anthony Dominijanni Mahesh Devarasetty Shay Soker Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance iScience Biological Sciences Cancer Bioengineering |
author_facet |
Anthony Dominijanni Mahesh Devarasetty Shay Soker |
author_sort |
Anthony Dominijanni |
title |
Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance |
title_short |
Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance |
title_full |
Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance |
title_fullStr |
Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance |
title_full_unstemmed |
Manipulating the Tumor Microenvironment in Tumor Organoids Induces Phenotypic Changes and Chemoresistance |
title_sort |
manipulating the tumor microenvironment in tumor organoids induces phenotypic changes and chemoresistance |
publisher |
Elsevier |
series |
iScience |
issn |
2589-0042 |
publishDate |
2020-12-01 |
description |
Summary: Tumors comprised a tightly surrounded tumor microenvironment, made up of non-cellular extracellular matrix (ECM) and stromal cells. Although treatment response is often attributed to tumor heterogeneity, progression and malignancy are profoundly influenced by tumor cell interactions with the surrounding ECM. Here, we used a tumor organoid model, consisting of hepatic stellate cells (HSCs) embedded in collagen type 1 (Col1) and colorectal cancer cell (HCT-116) spheroids, to determine the relationship between the ECM architecture, cancer cell malignancy, and chemoresistance. Exogenous transforming growth factor beta (TGF-β) used to activate the HSCs increased the remodeling and bundling of Col1 in the ECM around the cancer spheroid. A dense ECM architecture inhibited tumor cell growth, reversed their mesenchymal phenotype, preserved stem cell population, and reduced chemotherapy response. Overall, our results demonstrate that controlled biofabrication and manipulation of the ECM in tumor organoids results enables studying tumor cell-ECM interactions and better understand tumor cell response to chemotherapies. |
topic |
Biological Sciences Cancer Bioengineering |
url |
http://www.sciencedirect.com/science/article/pii/S2589004220310488 |
work_keys_str_mv |
AT anthonydominijanni manipulatingthetumormicroenvironmentintumororganoidsinducesphenotypicchangesandchemoresistance AT maheshdevarasetty manipulatingthetumormicroenvironmentintumororganoidsinducesphenotypicchangesandchemoresistance AT shaysoker manipulatingthetumormicroenvironmentintumororganoidsinducesphenotypicchangesandchemoresistance |
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