CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

Kun Mi,1 Zhihua Xing2 1Department of Biochemistry and Molecular Biology, Sichuan Cancer Hospital and Institute, 2Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Bac...

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Autores principales:	Mi K, Xing Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1e4f101f08194d6c9f60e66312041392
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spelling	oai:doaj.org-article:1e4f101f08194d6c9f60e663120413922021-12-02T08:07:25ZCD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold1178-2013https://doaj.org/article/1e4f101f08194d6c9f60e663120413922015-04-01T00:00:00Zhttp://www.dovepress.com/cd44cd24--breast-cancer-cells-exhibit-phenotypic-reversion-in-three-di-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kun Mi,1 Zhihua Xing2 1Department of Biochemistry and Molecular Biology, Sichuan Cancer Hospital and Institute, 2Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Self-assembling peptide nanofiber scaffolds have been shown to be a permissive biological material for tissue repair, cell proliferation, differentiation, etc. Recently, a subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells have different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16) peptide nanofiber scaffold compared with Matrigel® (BD Biosciences, Two Oak Park, Bedford, MA, USA) and collagen I.Methods: CD44 and CD24 expression was determined by flow cytometry. Cell proliferation was measured by 5-bromo-2'-deoxyuridine assay and DNA content measurement. Immunostaining was used to indicate the morphologies of cells in three-dimensional (3D) cultures of different scaffolds and the localization of β-catenin in the colonies. Western blot was used to determine the expression of signaling proteins. In vitro migration assay and inoculation into nude mice were used to evaluate invasion and tumorigenesis in vivo.Results: The breast cancer cell line MDA-MB-435S contained a high percentage (>99%) of CD44+/CD24- cells, which exhibited phenotypic reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel. The newly formed reverted acini-like colonies reassembled a basement membrane and reorganized their cytoskeletons. At the same time, cells cultured and embedded in RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different migration potential, which links their migration ability with their cellular morphology. Consistent with studies in vitro, the in vivo tumor formation assay further supported of the functional changes caused by the reversion in 3D RADA16 culture. Expression levels of intercellular surface adhesion molecule-1 were upregulated in cells cultured in RADA16 scaffolds, and the NF-kappa B inhibitor pyrrolidine dithiocarbamate could inhibit RADA16-induced upregulation of intercellular surface adhesion molecule-1 and the phenotype reversion of MDA-MB-453S cells.Conclusion: Culturing a CD44+/CD24--enriched breast cancer cell population in 3D RADA16 peptide nanofiber scaffold led to a significant phenotypic reversion compared with Matrigel and collagen I. Keywords: 3D culture, phenotype, reversionMi KXing ZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3043-3053 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Mi K Xing Z CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
description	Kun Mi,1 Zhihua Xing2 1Department of Biochemistry and Molecular Biology, Sichuan Cancer Hospital and Institute, 2Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Self-assembling peptide nanofiber scaffolds have been shown to be a permissive biological material for tissue repair, cell proliferation, differentiation, etc. Recently, a subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells have different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16) peptide nanofiber scaffold compared with Matrigel® (BD Biosciences, Two Oak Park, Bedford, MA, USA) and collagen I.Methods: CD44 and CD24 expression was determined by flow cytometry. Cell proliferation was measured by 5-bromo-2'-deoxyuridine assay and DNA content measurement. Immunostaining was used to indicate the morphologies of cells in three-dimensional (3D) cultures of different scaffolds and the localization of β-catenin in the colonies. Western blot was used to determine the expression of signaling proteins. In vitro migration assay and inoculation into nude mice were used to evaluate invasion and tumorigenesis in vivo.Results: The breast cancer cell line MDA-MB-435S contained a high percentage (>99%) of CD44+/CD24- cells, which exhibited phenotypic reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel. The newly formed reverted acini-like colonies reassembled a basement membrane and reorganized their cytoskeletons. At the same time, cells cultured and embedded in RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different migration potential, which links their migration ability with their cellular morphology. Consistent with studies in vitro, the in vivo tumor formation assay further supported of the functional changes caused by the reversion in 3D RADA16 culture. Expression levels of intercellular surface adhesion molecule-1 were upregulated in cells cultured in RADA16 scaffolds, and the NF-kappa B inhibitor pyrrolidine dithiocarbamate could inhibit RADA16-induced upregulation of intercellular surface adhesion molecule-1 and the phenotype reversion of MDA-MB-453S cells.Conclusion: Culturing a CD44+/CD24--enriched breast cancer cell population in 3D RADA16 peptide nanofiber scaffold led to a significant phenotypic reversion compared with Matrigel and collagen I. Keywords: 3D culture, phenotype, reversion
format	article
author	Mi K Xing Z
author_facet	Mi K Xing Z
author_sort	Mi K
title	CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
title_short	CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
title_full	CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
title_fullStr	CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
title_full_unstemmed	CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold
title_sort	cd44+/cd24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide rada16 nanofiber scaffold
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/1e4f101f08194d6c9f60e66312041392
work_keys_str_mv	AT mik cd44cd24breastcancercellsexhibitphenotypicreversioninthreedimensionalselfassemblingpeptiderada16nanofiberscaffold AT xingz cd44cd24breastcancercellsexhibitphenotypicreversioninthreedimensionalselfassemblingpeptiderada16nanofiberscaffold
_version_	1718398650177028096

CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

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