Cancer stem cell biology: from leukemia to solid tumors. Curr Opin Cell Biol

Division of Hematology/Oncology, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 703, Rochester, New York 14642, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 01/2005; 16(6):708-12. DOI: 10.1016/
Source: PubMed


The biology of stem cells and their intrinsic properties are now recognized as integral to tumor pathogenesis in several types of cancer. This observation has broad ramifications in the cancer research field and is likely to impact our understanding of the basic mechanisms of tumor formation and the strategies we use to treat cancers. A role for stem cells has been demonstrated for cancers of the hematopoietic system, breast and brain. Going forward it is likely that stem cells will also be implicated in other malignancies. Hence, a detailed understanding of stem cells and how they mediate tumor pathogenesis will be critical in developing more effective cancer therapies.

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Available from: Craig T. Jordan, Aug 06, 2014
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    • "Cancer stem cells (CSCs) are defined as cells that can self-renew, produce various types of progeny cells with more differentiated characteristics, and have a strong ability to drive continued expansion of malignant cells [78–80]. These properties of CSCs have similarities with those that define normal tissue stem cells. "
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    ABSTRACT: Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of "cell integrity" under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them.
    BioMed Research International 06/2012; 2012:903435. DOI:10.1155/2012/903435 · 2.71 Impact Factor
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    • "A growing body of evidence suggests the existence of cancer stem cells (CSCs), pluripotential stem cells that can perpetuate the generation or renewal of tumor forming cells in solid tumors [67]. The first evidence of cancer stem cells in sarcoma was reported in 2009. "
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    ABSTRACT: Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.
    Sarcoma 05/2012; 2012(3):849456. DOI:10.1155/2012/849456
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    • "First of all, the CSCs have normal stem cell properties such as self-renewal, differentiation, drug resistance and migration capacity. Then, the longevity of stem cells make them susceptible to accumulating genetic and epigenetic damages so as to make them good candidates for the emergence of neoplastic transformation [6], [7]. The CSCs are the only cells that are capable of generating tumours similar to the original patient specimens when transplanted into immunocompromised mice such as NOD/SCID mice [8]. "
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    ABSTRACT: Cancer Stem Cells (CSCs) hypothesis asserts that only a small subset of cells within a tumour is capable of both tumour initiation and sustainment. The Epithelial-Mesenchymal Transition (EMT) is an embryonic developmental program that is often activated during cancer invasion and metastasis. The aim of this study is to shed light on the relationship between EMT and CSCs by using LC31 lung cancer primary cell line. A549 and LC31 cell lines were treated with 2 ng/ml TGFβ-1 for 30 days, and 80 days, respectively. To evaluate EMT, morphological changes were assessed by light microscopy, immunofluorescence and cytometry for following markers: cytokeratins, e-cadherin, CD326 (epithelial markers) and CD90, and vimentin (mesenchymal markers). Moreover, RT-PCR for Slug, Twist and β-catenin genes were performed. On TGFβ-1 treated and untreated LC31 cell lines, we performed stemness tests such as pneumospheres growth and stem markers expression such as Oct4, Nanog, Sox2, c-kit and CD133. Western Blot for CD133 and tumorigenicity assays using NOD/SCID mice were performed. TGFβ-1 treated LC31 cell line lost its epithelial morphology assuming a fibroblast-like appearance. The same results were obtained for the A549 cell line (as control). Immunofluorescence and cytometry showed up-regulation of vimentin and CD90 and down-regulation of cytocheratin, e-cadherin and CD326 in TGFβ-1 treated LC31 and A549 cell lines. Slug, Twist and β-catenin m-RNA transcripts were up-regulated in TGFβ-1 treated LC31 cell line confirming EMT. This cell line showed also over-expression of Oct4, Nanog, Sox2 and CD133, all genes of stemness. In addition, in TGFβ-1 treated LC31 cell line, an increased pneumosphere-forming capacity and tumours-forming ability in NOD/SCID mice were detectable. The induction of EMT by TGFβ-1 exposure, in primary lung cancer cell line results in the acquisition of mesenchymal profile and in the expression of stem cell markers.
    PLoS ONE 06/2011; 6(6):e21548. DOI:10.1371/journal.pone.0021548 · 3.23 Impact Factor
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