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

• Published in: OncoTargets and therapy Vol. 8; no. default; pp. 323 - 334
• Main Authors: Nguyen, Sinh Truong, Nguyen, Huyen Lam, Pham, Viet Quoc, Nguyen, Giang Thuy, Tran, Cuong Do-Thanh, Phan, Ngoc Kim, Pham, Phuc Van
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Dove Medical Press
• Subjects: Breast cancer; Care and treatment; Dendritic cells; Drug resistance; Drug targeting; Genetic aspects; Health aspects; Innovations; Original Research; 4T1 cell line; breast tumor; dendritic cells; breast cancer stem cells; drug resistance; verapamil
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S77554

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.