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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 growth in mice in three different groups.Notes: The tumor size decreased from 8 to 15 days; however, in the BCSC-DC group, tumor size reduced more rapidly than in the control (RPMI 1640) and MSC-DC groups. (A) Tumor sizes were measured day by day from day 2 to 14. (B) Linear regression analysis of the slope from day 2 to 15.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.
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f6-ott-8-323: Tumor growth in mice in three different groups.Notes: The tumor size decreased from 8 to 15 days; however, in the BCSC-DC group, tumor size reduced more rapidly than in the control (RPMI 1640) and MSC-DC groups. (A) Tumor sizes were measured day by day from day 2 to 14. (B) Linear regression analysis of the slope from day 2 to 15.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.

Mentions: Although there is no significant difference in daily tumor size between the 4 groups, we observed differences in increasing and decreasing tumor size between treated and control (RPMI 1640) groups (Figure 6A). On the basis of linear regression, the slopes of the control and the MSC-DC groups were positive, and the slopes of the BCSC-DC groups were negative (Figure 5B). This suggests that the tumor size of the groups treated with DCs primed by BCSC antigens decreased faster than that of those treated with DCs primed by MSC antigens and the control group. Slope values (Δy/Δx) were 0.003159±0.005604, 0.02555±0.004868, and −0.003324±0.005297 in the control, MSC-DC, and BCSC-DC groups, respectively. The slopes were significantly different (P=0.0001337).


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 growth in mice in three different groups.Notes: The tumor size decreased from 8 to 15 days; however, in the BCSC-DC group, tumor size reduced more rapidly than in the control (RPMI 1640) and MSC-DC groups. (A) Tumor sizes were measured day by day from day 2 to 14. (B) Linear regression analysis of the slope from day 2 to 15.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

f6-ott-8-323: Tumor growth in mice in three different groups.Notes: The tumor size decreased from 8 to 15 days; however, in the BCSC-DC group, tumor size reduced more rapidly than in the control (RPMI 1640) and MSC-DC groups. (A) Tumor sizes were measured day by day from day 2 to 14. (B) Linear regression analysis of the slope from day 2 to 15.Abbreviations: BCSC, breast cancer stem cells; DC, dendritic cells; MSC, mesenchymal stem cells.
Mentions: Although there is no significant difference in daily tumor size between the 4 groups, we observed differences in increasing and decreasing tumor size between treated and control (RPMI 1640) groups (Figure 6A). On the basis of linear regression, the slopes of the control and the MSC-DC groups were positive, and the slopes of the BCSC-DC groups were negative (Figure 5B). This suggests that the tumor size of the groups treated with DCs primed by BCSC antigens decreased faster than that of those treated with DCs primed by MSC antigens and the control group. Slope values (Δy/Δx) were 0.003159±0.005604, 0.02555±0.004868, and −0.003324±0.005297 in the control, MSC-DC, and BCSC-DC groups, respectively. The slopes were significantly different (P=0.0001337).

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