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

PeerJ

article

Iuri C. Valadão¹  Ana Carolina L. Ralph¹  François Bordeleau²  Luciana M. Dzik¹  Karen S.C. Borbely³  Murilo V. Geraldo⁶  Cynthia A. Reinhart-King²  Vanessa M. Freitas¹ 

[1] Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo;Department of Biomedical Engineering, Vanderbilt University;Department of Immunology, Institute of Biomedical Sciences, University of São Paulo;Cell Biology Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas;Faculty of Nutrition, Federal University of Alagoas;Department of Structural and Functional Biology, Institute of Biology, University of Campinas

关键词: Breast cancer;    Cancer stem cells;    Type I collagen;    Mechanotransduction;    Extracellular matrix;   

DOI  :  10.7717/peerj.9153

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY