| | Progress in understanding melanoma propagationReceived 12 May 2010; received in revised form 15 June 2010; accepted 16 June 2010. published online 02 July 2010. Corrected Proof Abstract Melanoma, like most cancers, is a disease that wreaks havoc mostly through its propensity to spread and establish secondary tumors at sites that are anatomically distant from the primary tumor. The consideration of models of cancer progression is therefore important to understand the essence of this disease. Previous work has suggested that melanoma may propagate according to a cancer stem cell (CSC) model in which rare tumorigenic and bulk non-tumorigenic cells are organized into stable hierarchies within tumors. However, recent studies using assays that are more permissive for revealing tumorigenic potential indicate that it will not be possible to cure patients by focusing research and therapy on rare populations of cells within melanoma tumors. Studies of the nature of tumorigenic melanoma cells reveal that these cells may gain a growth, metastasis and/or therapy resistance advantage by acquiring new genetic mutations and by reversible epigenetic mechanisms. In this light, efforts to link the phenotypes, genotypes and epigenotypes of melanoma cells with differences in their in vivo malignant potential provide the greatest hope of advancing the exciting progress finally being made against this disease. a Melanoma Research Laboratory and Department of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne 3002, Australia b Department of Pathology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville 3010, Australia c Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA Corresponding author. Melanoma Research Laboratory and Department of Hematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne 3002, Australia. Tel.: +61 3 9656 5235; fax: +61 3 9656 1411.
PII: S1574-7891(10)00054-2 doi:10.1016/j.molonc.2010.06.006 Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved. | |
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