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Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations

Escrito por Carla Brito Lopes

Abstract: Breast cancer is a leading cause of death in women, and almost all complications are due to chemotherapy resistance. Drug-resistant cells with stem cell phenotypes are thought to cause failure in breast cancer chemotherapy. Dendritic cell (DC) therapy is a potential approach to eradicate these cells.

This study evaluates the specificity of DCs for breast cancer stem cells (BCSCs) in vitro and in vivo. BCSCs were enriched by a verapamil-resistant screening method, and reconfirmed by ALDH expression analysis and mammosphere assay. Mesenchymal stem cells (MSCs) were isolated from allogeneic murine bone marrow.

DCs were induced from bone marrow-derived monocytes with 20 ng/mL GC-MSF and 20 ng/mL IL-4. Immature DCs were primed with BCSC- or MSC-derived antigens to make two kinds of mature DCs: BCSC-DCs and MSC-DCs, respectively. In vitro ability of BCSC-DCs and MSC-DCs with cytotoxic T lymphocytes (CTLs) to inhibit BCSCs was tested using the xCELLigence technique.

In vivo, BCSC-DCs and MSC-DCs were transfused into the peripheral blood of BCSC tumor-bearing mice. The results show that in vitro BCSC-DCs significantly inhibited BCSC proliferation at a DC:CTL ratio of 1:40, while MSC-DCs nonsignificantly decreased BCSC proliferation. In vivo, tumor sizes decreased from 18.8% to 23% in groups treated with BCSC-DCs; in contrast, tumors increased 14% in the control group (RPMI 1640) and 47% in groups treated with MSC-DCs.

The results showed that DC therapy could target and be specific to BCSCs. DCs primed with MSCs could trigger tumor growth. These results also indicate that DCs may be a promising therapy for treating drug-resistant cancer cells as well as cancer stem cells.

Keywords: dendritic cells, 4T,1 cell line, breast tumor, breast cancer stem cells, verapamil, drug resistance


 

Article first published: 30 January 2015
doi:  http://dx.doi.org/10.2147/OTT.S77554
URL: Download Article [PDF]

Citation: [Nguyen ST, Nguyen HL, Pham VQ, Nguyen GT, Tran CD, Phan NK, Pham PV. Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations. OncoTargets and Therapy 2015:8 323–334]

Copyright: © 2015 Nguyen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/.

Sobre o autor

Carla Brito Lopes

Carla nasceu a 14 de Fevereiro de 1977 em Viana do Castelo. Completou o bacharelato em Anatomia Patológica, Citológica e Tanatológica na ESTES-Porto em 1998 e licenciou-se em 2001 pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016.
Actualmente encontra-se a frequentar mestrado em Genética Molecular e Biomedicina na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa.