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Stem Cells International
Volume 2016, Article ID 3631764, 13 pages
Review Article

Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

1Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London WC2A 3LY, UK
2Central University Hospital of Asturias (HUCA) and Institute of Oncology of Asturias (IUOPA), 33011 Oviedo, Spain
3Complutense University of Madrid, 28040 Madrid, Spain
4Orthopaedic Pathophysiology and Regenerative Medicine Unit, Rizzoli Orthopaedic Institute, 40136 Bologna, Italy
5Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy
6Cellular Biotechnology Laboratory, Institute of Health Carlos III (ISCIII), Majadahonda, 28220 Madrid, Spain

Received 7 January 2016; Accepted 10 May 2016

Academic Editor: Andrzej Lange

Copyright © 2016 Ander Abarrategi 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.


Osteosarcoma (OS) is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.