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      Metformin: An Emerging New Therapeutic Option for Targeting Cancer Stem Cells and Metastasis

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          Abstract

          Metastasis is an intricate process by which a small number of cancer cells from the primary tumor site undergo numerous alterations, which enables them to form secondary tumors at another and often multiple sites in the host. Transition of a cancer cell from epithelial to mesenchymal phenotype is thought to be the first step in the progression of metastasis. Recently, the recognition of cancer stem cells has added to the perplexity in understanding metastasis, as studies suggest cancer stem cells to be the originators of metastasis. All current and investigative drugs have been unable to prevent or reverse metastasis, as a result of which most metastatic cancers are incurable. A potential drug that can be considered is metformin, an oral hypoglycemic drug. In this review we discuss the potential of metformin in targeting both epithelial to mesenchymal transition and cancer stem cells in combating cancer metastases.

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          Most cited references89

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Human induced pluripotent stem cells free of vector and transgene sequences.

            Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. We describe the derivation of human iPS cells with the use of nonintegrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. These results demonstrate that reprogramming human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors and removes one obstacle to the clinical application of human iPS cells.
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              Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.

              The dissemination of tumour cells is the prerequisite of metastases and is correlated with a loss of epithelial differentiation and the acquisition of a migratory phenotype, a hallmark of malignant tumour progression. A stepwise, irreversible accumulation of genetic alterations is considered to be the responsible driving force. But strikingly, metastases of most carcinomas recapitulate the organization of their primary tumours. Although current models explain distinct and important aspects of carcinogenesis, each alone can not explain the sum of the cellular changes apparent in human cancer progression. We suggest an extended, integrated model that is consistent with all aspects of human tumour progression - the 'migrating cancer stem (MCS)-cell' concept.
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                Author and article information

                Journal
                J Oncol
                J Oncol
                JO
                Journal of Oncology
                Hindawi Publishing Corporation
                1687-8450
                1687-8469
                2012
                4 June 2012
                : 2012
                : 928127
                Affiliations
                1Division of Gynecology Oncology, Department of Women's Health Services, Henry Ford Health System, Detroit, MI 48202, USA
                2Departments of Pathology and Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA
                Author notes
                *Ramandeep Rattan: rrattan1@ 123456hfhs.org

                Academic Editor: Pierre Savagner

                Article
                10.1155/2012/928127
                3373168
                22701483
                74dd8feb-763d-46c1-af9b-590897922954
                Copyright © 2012 Ramandeep Rattan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 December 2011
                : 5 March 2012
                Categories
                Review Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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