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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

Tumor mass harvested from mice on day 15. After sacrificing mice, tumors were collected by surgery.Notes: (A) Tumor from one mouse of control group where DCs were intravenously primed with MSC antigens (MSC-DC). (B) Tumors from all groups. Line I is from DCs intravenously primed with MSC antigens (MSC-DC), line II is from the control (RPMI 1640), line III is from DCs intravenously primed with BCSC antigen (BCSC-DC). The arrow indicates a tumor.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.
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f7-ott-8-323: Tumor mass harvested from mice on day 15. After sacrificing mice, tumors were collected by surgery.Notes: (A) Tumor from one mouse of control group where DCs were intravenously primed with MSC antigens (MSC-DC). (B) Tumors from all groups. Line I is from DCs intravenously primed with MSC antigens (MSC-DC), line II is from the control (RPMI 1640), line III is from DCs intravenously primed with BCSC antigen (BCSC-DC). The arrow indicates a tumor.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.

Mentions: The data can provide more evidence about changing tumor size when comparing tumor size between days 2 and 15 (Figure 7). Tumor size decreased 23% in the BCSC-DC groups. In contrast, tumor size increased 14% in the control group; in particular, in the MSC-DC group, tumor size increased 47%. This indicates that therapeutic treatment with DCs primed by BCSC-derived antigens is effective in decreasing tumor size. Moreover, DCs primed by MSC antigen actually caused tumor mass to increase.


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)

Tumor mass harvested from mice on day 15. After sacrificing mice, tumors were collected by surgery.Notes: (A) Tumor from one mouse of control group where DCs were intravenously primed with MSC antigens (MSC-DC). (B) Tumors from all groups. Line I is from DCs intravenously primed with MSC antigens (MSC-DC), line II is from the control (RPMI 1640), line III is from DCs intravenously primed with BCSC antigen (BCSC-DC). The arrow indicates a tumor.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ott-8-323: Tumor mass harvested from mice on day 15. After sacrificing mice, tumors were collected by surgery.Notes: (A) Tumor from one mouse of control group where DCs were intravenously primed with MSC antigens (MSC-DC). (B) Tumors from all groups. Line I is from DCs intravenously primed with MSC antigens (MSC-DC), line II is from the control (RPMI 1640), line III is from DCs intravenously primed with BCSC antigen (BCSC-DC). The arrow indicates a tumor.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.
Mentions: The data can provide more evidence about changing tumor size when comparing tumor size between days 2 and 15 (Figure 7). Tumor size decreased 23% in the BCSC-DC groups. In contrast, tumor size increased 14% in the control group; in particular, in the MSC-DC group, tumor size increased 47%. This indicates that therapeutic treatment with DCs primed by BCSC-derived antigens is effective in decreasing tumor size. Moreover, DCs primed by MSC antigen actually caused tumor mass to increase.

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