High type I collagen density fails to increase breast cancer stem cell phenotype

Breast cancer is a highly frequent and lethal malignancy which metastasis and relapse frequently associates with the existence of breast cancer stem cells (CSCs). CSCs are undifferentiated, aggressive and highly resistant to therapy, with traits modulated by microenvironmental cells and the extracel...

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Main Authors: Iuri C. Valadão, Ana Carolina L. Ralph, François Bordeleau, Luciana M. Dzik, Karen S.C. Borbely, Murilo V. Geraldo, Cynthia A. Reinhart-King, Vanessa M. Freitas
Format: Article
Language:English
Published: PeerJ Inc. 2020-05-01
Series:PeerJ
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Online Access:https://peerj.com/articles/9153.pdf
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author Iuri C. Valadão
Ana Carolina L. Ralph
François Bordeleau
Luciana M. Dzik
Karen S.C. Borbely
Murilo V. Geraldo
Cynthia A. Reinhart-King
Vanessa M. Freitas
author_facet Iuri C. Valadão
Ana Carolina L. Ralph
François Bordeleau
Luciana M. Dzik
Karen S.C. Borbely
Murilo V. Geraldo
Cynthia A. Reinhart-King
Vanessa M. Freitas
author_sort Iuri C. Valadão
collection DOAJ
description Breast cancer is a highly frequent and lethal malignancy which metastasis and relapse frequently associates with the existence of breast cancer stem cells (CSCs). CSCs are undifferentiated, aggressive and highly resistant to therapy, with traits modulated by microenvironmental cells and the extracellular matrix (ECM), a biologically complex and dynamic structure composed mainly by type I collagen (Col-I). Col-I enrichment in the tumor-associated ECM leads to microenvironment stiffness and higher tumor aggressiveness and metastatic potential. While Col-I is also known to induce tumor stemness, it is unknown if such effect is dependent of Col-I density. To answer this question, we evaluated the stemness phenotype of MDA-MB-231 and MCF-7 human breast cancer cells cultured within gels of varying Col-I densities. High Col-I density increased CD44+CD24− breast cancer stem cell (BCSC) immunophenotype but failed to potentiate Col-I fiber alignment, cell self-renewal and clonogenicity in MDA-MB-231 cells. In MCF-7 cells, high Col-I density decreased total levels of variant CD44 (CD44v). Common to both cell types, high Col-I density induced neither markers related to CSC nor those related with mechanically-induced cell response. We conclude that high Col-I density per se is not sufficient to fully develop the BCSC phenotype.
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spelling doaj.art-1e0ac16b7741462d92bda7bffd6291cb2023-12-02T21:50:04ZengPeerJ Inc.PeerJ2167-83592020-05-018e915310.7717/peerj.9153High type I collagen density fails to increase breast cancer stem cell phenotypeIuri C. Valadão0Ana Carolina L. Ralph1François Bordeleau2Luciana M. Dzik3Karen S.C. Borbely4Murilo V. Geraldo5Cynthia A. Reinhart-King6Vanessa M. Freitas7Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USADepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USADepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilBreast cancer is a highly frequent and lethal malignancy which metastasis and relapse frequently associates with the existence of breast cancer stem cells (CSCs). CSCs are undifferentiated, aggressive and highly resistant to therapy, with traits modulated by microenvironmental cells and the extracellular matrix (ECM), a biologically complex and dynamic structure composed mainly by type I collagen (Col-I). Col-I enrichment in the tumor-associated ECM leads to microenvironment stiffness and higher tumor aggressiveness and metastatic potential. While Col-I is also known to induce tumor stemness, it is unknown if such effect is dependent of Col-I density. To answer this question, we evaluated the stemness phenotype of MDA-MB-231 and MCF-7 human breast cancer cells cultured within gels of varying Col-I densities. High Col-I density increased CD44+CD24− breast cancer stem cell (BCSC) immunophenotype but failed to potentiate Col-I fiber alignment, cell self-renewal and clonogenicity in MDA-MB-231 cells. In MCF-7 cells, high Col-I density decreased total levels of variant CD44 (CD44v). Common to both cell types, high Col-I density induced neither markers related to CSC nor those related with mechanically-induced cell response. We conclude that high Col-I density per se is not sufficient to fully develop the BCSC phenotype.https://peerj.com/articles/9153.pdfBreast cancerCancer stem cellsType I collagenMechanotransductionExtracellular matrix
spellingShingle Iuri C. Valadão
Ana Carolina L. Ralph
François Bordeleau
Luciana M. Dzik
Karen S.C. Borbely
Murilo V. Geraldo
Cynthia A. Reinhart-King
Vanessa M. Freitas
High type I collagen density fails to increase breast cancer stem cell phenotype
PeerJ
Breast cancer
Cancer stem cells
Type I collagen
Mechanotransduction
Extracellular matrix
title High type I collagen density fails to increase breast cancer stem cell phenotype
title_full High type I collagen density fails to increase breast cancer stem cell phenotype
title_fullStr High type I collagen density fails to increase breast cancer stem cell phenotype
title_full_unstemmed High type I collagen density fails to increase breast cancer stem cell phenotype
title_short High type I collagen density fails to increase breast cancer stem cell phenotype
title_sort high type i collagen density fails to increase breast cancer stem cell phenotype
topic Breast cancer
Cancer stem cells
Type I collagen
Mechanotransduction
Extracellular matrix
url https://peerj.com/articles/9153.pdf
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