Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine

Winquist, Raymond J.; Boucher, Diane M.; Wood, Mark; Furey, Brinley F.

doi:10.1016/j.bcp.2009.03.020

Cited by 43 publications

(25 citation statements)

References 67 publications

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“…Therefore, according to CSCs model (26,27), targeting the minor population of CSCs may be a effective and curative therapeutic strategy for eradicating cancer. Here, we sorted CD133 + cells from SMMC-7721 cells, which demonstrated many CSCs-like properties.…”

Section: Discussionmentioning

confidence: 99%

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

Zhang

Luo²,

Luo³

et al. 2011

Int J Oncol

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Abstract. MicroRNAs (miRNAs) have been implicated in the maintenance of the cancer stem cell (CSC) phenotype via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Here, we compared the miRNA profiles of CD133 + and CD133 -primary hepatocellular carcinoma (HCC) subpopulations and found upregulation of 5 miRNAs in CD133 -subpopulations, including hsa-miR-150, which may be involved in maintenance of the CD133 + liver CSC phenotype. We also show that miR-150 interacts with the 3'UTR of c-Myb mRNA and overexpression of miR-150 downregulates c-Myb protein levels. Furthermore, overexpression of miR-150 lead to a significant reduction of CD133 + cells, accompanied by significant inhibition of cell growth and tumorsphere formation. In addition, overexpression of miR-150 induces cell cycle arrest and apoptosis in CD133 + cells. Consistent with the outcome of cell cycle arrest and cell apoptosis, Western blotting results demonstrate that the cell cycle regulator cyclin D1 and cell survival regulator Bcl-2 are decreased in cells transfected with miR-150. Collectively, our findings demonstrate for the first time that miR-150 may be involved in liver CSC self-renewal, potentially via modulation of the downstream target c-Myb.

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Section: Discussionmentioning

confidence: 99%

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

Zhang

Luo²,

Luo³

et al. 2011

Int J Oncol

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show abstract

“…Although some targeting of stem cell molecular pathways, such as Hedgehog, Notch, and b-catenin, have been initiated in clinical trials, 57 immunotherapy largely has ignored the CSC phenomenon. Moreover, the evaluation of CSCs in the context of host-immune responses largely has been disregarded, and most studies on CSCs have been done using immunocompromised rodent models.…”

Section: Challenges For Peptide Vaccination Strategiesmentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

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“…Too often initial beneficial responses in (bone) metastases are followed by re-growth of therapy-resistant malignant lesions (Winquist et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation

et al. 2011

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Accumulating evidence suggests that a subpopulation of breast cancer cells, referred to as cancer stem cells (CSCs), have the ability to propagate a tumor and potentially seed new metastases. Furthermore, stimulation of an epithelialto-mesenchymal transition by factors like transforming growth factor-b (TGFb) is accompanied with the generation of breast CSCs. Previous observations indicated that bone morphogenetic protein-7 (BMP7) antagonizes the protumorigenic and prometastatic actions of TGFb, but whether BMP7 action is mechanistically linked to breast CSCs has remained elusive. Here, we have studied the effects of BMP7, BMP2 and a BMP2/7 heterodimer on the formation of human breast CSCs (ALDH hi /CD44 hi / CD24 À/low ) and bone metastases formation in a preclinical model of intra-cardiac injection of MDA-MB-231 cells in athymic nude (Balb/c nu/nu) mice. The BMP2/7 heterodimer was the most efficient stimulator of BMP signaling and very effectively reduced TGFb-driven Smad signaling and cancer cell invasiveness. The tested BMPs-particularly the heterodimeric BMP2/7-strongly reduced the size of the ALDH hi /CD44 hi /CD24 À/low CSC subpopulation. In keeping with these in vitro observations, pretreatment of cancer cells with BMPs for 72 h prior to systemic inoculation of the cancer cells inhibited the formation of bone metastases. Collectively, our data support the notion that breast CSCs are involved in bone metastasis formation and describe heterodimeric BMP2/7 as a powerful TGFb antagonist with anti-metastatic potency.

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Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine

Cited by 43 publications

References 67 publications

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

A new era in anticancer peptide vaccines

The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation

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