Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas

Salerno,Manuela; Avnet,Sofia; Bonuccelli,Gloria; Eramo,Adriana; De Maria,Ruggero; Gambarotti,Marco; Gamberi,Gabriella; Baldini,Nicola

doi:10.3892/ijo.2013.1927

Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas

Authors:
- Manuela Salerno
- Sofia Avnet
- Gloria Bonuccelli
- Adriana Eramo
- Ruggero De Maria
- Marco Gambarotti
- Gabriella Gamberi
- Nicola Baldini
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Affiliations: Department of Orthopaedic Pathophysiology and Regenerative Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy, Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy, Regina Elena Cancer Institute, Rome, Italy, Department of Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy
Published online on: May 1, 2013 https://doi.org/10.3892/ijo.2013.1927
Pages: 95-102

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Abstract

Musculoskeletal sarcomas are aggressive malignancies often characterized by an adverse prognosis despite the use of intense multiagent chemotherapy or molecular targeted therapy in combination to surgery and radiotherapy. Stem-like cells identified within solid tumors have been recently implicated in drug resistance, metastasis and local relapse. Here, we report the identification of putative cancer stem cells (CSCs) in sarcomas using a sphere culture system. These sarcospheres, able to grow in anchorage-independent and serum-starved conditions, express the pluripotent embryonic stem cell marker genes OCT3/4, Nanog and SOX2. Expression levels of these genes were greater in sarcospheres than in the parental tumor cultures. Importantly, the isolated tumor spheres transplanted into mice were tumorigenic and capable of recapitulating the human disease. Finally, we demonstrated that low (1%) O2 conditions, reproducing those found within the tumor microenvironment, significantly increase the number and the size of sarcospheres. The sphere formation assay is, therefore, a valuable method for the isolation of putative CSCs from human sarcomas and its efficiency is improved by controlling oxygen availability. This method provides a reliable preclinical model that can be used for future studies aimed at investigating crucial aspects of sarcoma biology, such as resistance to treatments and relapse.

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