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

Nguyen ST, Nguyen HL, Pham VQ, Nguyen GT, Tran CD, Phan NK, Pham PV - Onco Targets Ther (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam.

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.

No MeSH data available.


Related in: MedlinePlus

Selection of verapamil-resistant 4T1 cells.Notes: Effect of verapamil on the proliferation of 4T1 mouse mammary cancer cell line within 140 hours, with various verapamil concentrations (0–100 μg/mL) in RPMI-10% FBS medium at a density of 5,000 cells/well (A). The morphology of 4T1 cells before (B) and after (C) 48 hours of incubation in 50 μg/mL verapamil.Abbreviation: FBS, fetal bovine serum.
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f1-ott-8-323: Selection of verapamil-resistant 4T1 cells.Notes: Effect of verapamil on the proliferation of 4T1 mouse mammary cancer cell line within 140 hours, with various verapamil concentrations (0–100 μg/mL) in RPMI-10% FBS medium at a density of 5,000 cells/well (A). The morphology of 4T1 cells before (B) and after (C) 48 hours of incubation in 50 μg/mL verapamil.Abbreviation: FBS, fetal bovine serum.

Mentions: In groups with 10–40 μg/mL verapamil, cancer cells proliferated more slowly than in the control (0 μg/mL verapamil). Alternatively, at 60–100 μg/mL levels of verapamil, cancer cells were completely inhibited after 20 hours of treatment, and cell growth rates dramatically decreased and the cells died (Figure 1A). At 50 μg/mL verapamil, cancer cells were also inhibited after 20 hours of treatment, but there were a few living cells, so these populations continued to develop and formed verapamil-resistant cell populations. This concentration of verapamil was used to develop VRCs for the next experiment.


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

Nguyen ST, Nguyen HL, Pham VQ, Nguyen GT, Tran CD, Phan NK, Pham PV - Onco Targets Ther (2015)

Selection of verapamil-resistant 4T1 cells.Notes: Effect of verapamil on the proliferation of 4T1 mouse mammary cancer cell line within 140 hours, with various verapamil concentrations (0–100 μg/mL) in RPMI-10% FBS medium at a density of 5,000 cells/well (A). The morphology of 4T1 cells before (B) and after (C) 48 hours of incubation in 50 μg/mL verapamil.Abbreviation: FBS, fetal bovine serum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321654&req=5

f1-ott-8-323: Selection of verapamil-resistant 4T1 cells.Notes: Effect of verapamil on the proliferation of 4T1 mouse mammary cancer cell line within 140 hours, with various verapamil concentrations (0–100 μg/mL) in RPMI-10% FBS medium at a density of 5,000 cells/well (A). The morphology of 4T1 cells before (B) and after (C) 48 hours of incubation in 50 μg/mL verapamil.Abbreviation: FBS, fetal bovine serum.
Mentions: In groups with 10–40 μg/mL verapamil, cancer cells proliferated more slowly than in the control (0 μg/mL verapamil). Alternatively, at 60–100 μg/mL levels of verapamil, cancer cells were completely inhibited after 20 hours of treatment, and cell growth rates dramatically decreased and the cells died (Figure 1A). At 50 μg/mL verapamil, cancer cells were also inhibited after 20 hours of treatment, but there were a few living cells, so these populations continued to develop and formed verapamil-resistant cell populations. This concentration of verapamil was used to develop VRCs for the next experiment.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam.

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.

No MeSH data available.


Related in: MedlinePlus