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Title:
Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy | Journal of Translational Medicine
Description:
Background Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs). Methods We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.
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Keywords {π}
cells, cancer, bcscs, breast, cell, knockdown, pubmed, article, google, scholar, stem, expression, cas, nonbcscs, cdcd, differentiation, tumors, mice, resistance, gene, figure, genes, central, therapy, cycle, genebanknm, study, phase, compared, stemness, downregulation, similar, signaling, reduced, human, authors, analysis, targeting, metastasis, potential, treatment, population, pathway, flow, muc, pathways, populations, cytometry, myc, original,
Topics {βοΈ}
cancer stem-cell-targeting therapy g1/s-specific ccnd1 gene patched/hedgehog/smoothened signalling pathway voltage-dependent anion channel stem/progenitor cell properties article download pdf her2-positive breast cancer df3/muc1 breast carcinoma anterior-posterior axis formation nonpeptidic small-molecule antagonists fatty acid synthase mammary stem cells stem cell-related genes gastric-tumor-bearing mice [46] high tumor-causing potential magnetic-activated cell sorting pi3k/akt signaling pathway anti-tumor agent doxorubicin anti-tumor drug resistance nod/scid mouse model trans retinoic acid human mammary gland stem cell differentiation stem cell research resveratrol suppresses growth lower tumor-causing potential anti-biotin microbeads p53-mediated apoptosis cd44+cd24- cell populations cd44-cd24- cell populations small hairpin rna vitro reverse-transcription pcr anti-cd24-fluorescein isothiocyanate cancer stem cells her2-targeting agents reduced fatty acid synthesis her2-targeted agents relapse mcf-7 cell lines human breast cancer stem cells exhibit transcription factor hsf1 promising differentiation therapy anti-cd24-biotin mammary epithelial cells breast cancer research stem cell phenotype genetic analysis system privacy choices/manage cookies isolate cd44+cd24+ cells cell cycle changed
Questions {β}
- Calderwood SK: Heat shock proteins in breast cancer progression--a suitable case for treatment?
- Lupu R, Menendez JA: Targeting fatty acid synthase in breast and endometrial cancer: An alternative to selective estrogen receptor modulators?
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headline:Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy
description:Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs). We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.
datePublished:2011-12-07T00:00:00Z
dateModified:2011-12-07T00:00:00Z
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Breast cancer stem cells
Breast cancer cells
CD44
Differentiation
Differentiation therapy
Knockdown
Biomedicine
general
Medicine/Public Health
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headline:Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy
description:Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs). We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.
datePublished:2011-12-07T00:00:00Z
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Breast cancer stem cells
Breast cancer cells
CD44
Differentiation
Differentiation therapy
Knockdown
Biomedicine
general
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