Overview of Cancer Stem Cells (CSCs) and Mechanisms of Their Regulation: Implications for Cancer Therapy

Bin Bao1, Aamir Ahmad1, Asfar S. Azmi1, Shadan Ali2, Fazlul H. Sarkar2

1 Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, 2 Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 14.25
DOI:  10.1002/0471141755.ph1425s61
Online Posting Date:  June, 2013
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The identification of small subpopulations of cancer stem cells (CSCs) from blood mononuclear cells in human acute myeloid leukemia (AML) in 1997 was a landmark observation that recognized the potential role of CSCs in tumor aggressiveness. Two critical properties contribute to the functional role of CSCs in the establishment and recurrence of cancerous tumors: their capacity for self‐renewal and their potential to differentiate into unlimited heterogeneous populations of cancer cells. These findings suggest that CSCs may represent novel therapeutic targets for the treatment and/or prevention of tumor progression, since they appear to be involved in cell migration, invasion, metastasis, and treatment resistance–all of which lead to poor clinical outcomes. The identification of CSC‐specific markers, the isolation and characterization of CSCs from malignant tissues, and targeting strategies for the destruction of CSCs provide a novel opportunity for cancer research. This overview describes the potential implications of several common CSC markers in the identification of CSC subpopulations that are restricted to common malignant diseases, e.g., leukemia, and breast, prostate, pancreatic, and lung cancers. The role of microRNAs (miRNAs) in the regulation of CSC function is also discussed, as are several methods commonly used in CSC research. The potential role of the antidiabetic drug metformin– which has been shown to have effects on CSCs, and is known to function as an antitumor agent–is discussed as an example of this new class of chemotherapeutics.Curr. Protoc. Pharmacol. 61:14.25.1‐14.25.14 © 2013 by John Wiley & Sons, Inc.

Keywords: CSCs; cell surface markers; miRNAs; metformin

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Table of Contents

  • Introduction
  • CSCs and Tumor Aggressiveness
  • Identification of CSC Markers in Common Malignant Diseases
  • The Role of miRNAs in the Regulation of CSC Characteristics
  • Common Experimental Methods Used in CSC Research
  • The Antidiabetic Drug Metformin as a Potential Antitumor Agent Targeting CSC Subpopulations
  • Perspective and Conclusion
  • Acknowledgements
  • Figures
  • Tables
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