The Increasing Complexity of the Cancer Stem Cell Paradigm

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Science (Impact Factor: 33.61). 07/2009; 324(5935):1670-3. DOI: 10.1126/science.1171837
Source: PubMed

ABSTRACT The investigation and study of cancer stem cells (CSCs) have received enormous attention over the past 5 to 10 years but remain
topics of considerable controversy. Opinions about the validity of the CSC hypothesis, the biological properties of CSCs,
and the relevance of CSCs to cancer therapy differ widely. In the following commentary, we discuss the nature of the debate,
the parameters by which CSCs can or cannot be defined, and the identification of new potential therapeutic targets elucidated
by considering cancer as a problem in stem cell biology.

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Available from: Craig T. Jordan, Dec 30, 2014
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    • "Therefore, CSCs stand at the apex of a tumor cell hierarchy. They resemble functional similarities to normal somatic stem cells, that is, hematopoietic stem cells (HSCs) with their capacity to renew themselves and to give rise to all mature blood cell lineages [14] [15]. A common terminology for cells with specific properties in ALL used in this review should be introduced: the leukemic cell of origin (LCO) is the first cell carrying the initial preleukemic lesion. "
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    ABSTRACT: Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients' outcome in ALL.
    Stem cell International 08/2015; 2015:137164. DOI:10.1155/2015/137164 · 2.81 Impact Factor
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    • "Various factors result in drug resistance, such as genetic mutation, metabolic changes and cancer stem cells (CSCs). CSCs are a small population of cancer cells within tumors, with an ability to self-renew and give rise to progeny that differentiate into diverse tumor cells to drive tumorigenesis (Rosen and Jordan 2009). Although the hypothesis of CSCs has been put forward from a long time ago, the actual existence of CSCs was experimentally proven in the early 1990s on the basis of advances in study of cell surface markers of stem cells (Spangrude et al. 1988). "
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    ABSTRACT: Despite standard cancer therapies such as chemotherapy and targeted therapy have shown some efficacies, the cancer in many cases eventually relapses and metastasizes upon stopping the treatment. There is a small subpopulation of cancer cells within tumor, with specific characters similar to those found in stem cells. This group of cancer cells is known as tumor-initiating or cancer stem cells (CSCs), which have an ability to self-renew and give rise to cancer cell progeny. CSCs are related with drug resistance, metastasis and relapse of cancer, hence emerging as a crucial drug target for eliminating cancer. Rapid advancement of CSC biology has enabled researchers to isolate and culture CSCs in vitro, making the cells amenable to high-throughput drug screening. Recently, drug repositioning, which utilizes existing drugs to develop potential new indications, has been gaining popularity as an alternative approach for the drug discovery. As existing drugs have favorable bioavailability and safety profiles, drug repositioning is now actively exploited for prompt development of therapeutics for many serious diseases, such as cancer. In this review, we will introduce latest examples of attempted drug repositioning targeting CSCs and discuss potential use of the repositioned drugs for cancer therapy.
    Archives of Pharmacal Research 07/2015; 38(9). DOI:10.1007/s12272-015-0628-1 · 2.05 Impact Factor
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    • "In addition to selfrenewal and differentiation capabilities, CSCs also seed tumors when transplanted into a host animal. The CSCs can be distinguished from other cells within the tumor by evaluating the symmetry of its cell division and changes in gene expression [4] [5]. Hyperthermia (HPT) is an approach that promotes a rise in temperature at the biological site. "
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    ABSTRACT: The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle. The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.
    Journal of Magnetism and Magnetic Materials 04/2015; 380:372–376. DOI:10.1016/j.jmmm.2014.10.098 · 1.97 Impact Factor
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