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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

Mesenchymal stem cells isolated from bone marrow.Notes: These cells exhibited the mesenchymal stem cell particular phenotype such as negative with CD14, CD34, and CD45 (A–C), positive with CD44, CD73, CD90, and CD105 (D–G), fibroblast-like shape (H), successful differentiation into adipocytes that stained positive with Oil red staining (I), osteoblasts that stained positive with Alizarin red (J).Abbreviations: FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.
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f3-ott-8-323: Mesenchymal stem cells isolated from bone marrow.Notes: These cells exhibited the mesenchymal stem cell particular phenotype such as negative with CD14, CD34, and CD45 (A–C), positive with CD44, CD73, CD90, and CD105 (D–G), fibroblast-like shape (H), successful differentiation into adipocytes that stained positive with Oil red staining (I), osteoblasts that stained positive with Alizarin red (J).Abbreviations: FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.

Mentions: After 24 hours of incubation, some mononuclear cells attached to the flask surfaces and exhibited the fibroblast-like shape (Figure 3H). These cells rapidly proliferated after 96 hours. These cells exhibited some properties of MSCs, such as positive expression of CD44, CD73, CD90, and CD105 (Figure 3D–G), but no expression of CD14, CD34, and CD45 (Figure 3A–C). These cells also successfully differentiated into adipocytes that stained with Oil red, and osteoblasts that stained with Alizarin red (Figure 3I, J). These cells continuously proliferated for five passages and were used for further experiments.


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)

Mesenchymal stem cells isolated from bone marrow.Notes: These cells exhibited the mesenchymal stem cell particular phenotype such as negative with CD14, CD34, and CD45 (A–C), positive with CD44, CD73, CD90, and CD105 (D–G), fibroblast-like shape (H), successful differentiation into adipocytes that stained positive with Oil red staining (I), osteoblasts that stained positive with Alizarin red (J).Abbreviations: FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ott-8-323: Mesenchymal stem cells isolated from bone marrow.Notes: These cells exhibited the mesenchymal stem cell particular phenotype such as negative with CD14, CD34, and CD45 (A–C), positive with CD44, CD73, CD90, and CD105 (D–G), fibroblast-like shape (H), successful differentiation into adipocytes that stained positive with Oil red staining (I), osteoblasts that stained positive with Alizarin red (J).Abbreviations: FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.
Mentions: After 24 hours of incubation, some mononuclear cells attached to the flask surfaces and exhibited the fibroblast-like shape (Figure 3H). These cells rapidly proliferated after 96 hours. These cells exhibited some properties of MSCs, such as positive expression of CD44, CD73, CD90, and CD105 (Figure 3D–G), but no expression of CD14, CD34, and CD45 (Figure 3A–C). These cells also successfully differentiated into adipocytes that stained with Oil red, and osteoblasts that stained with Alizarin red (Figure 3I, J). These cells continuously proliferated for five passages and were used for further experiments.

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