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Int. J. Mol. Sci. 2018, 19(3), 707; https://doi.org/10.3390/ijms19030707

Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma

1
Laboratoire d’étude des sarcomes osseux et remodelage des tissus calcifiés, INSERM UMR 1238, Université de Nantes, PhyOS, 44034 Nantes CEDEX 1, France
2
Centre Hospitalier Régional Universitaire de Tours, Service de Chirurgie Orthopédique 2, Faculté de Médecine de Tours, Université de Tours, 37044 CEDEX 9 Tours, France
3
Harvard School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
4
STROMA Lab, INSERM U1031, Etablissement Français du Sang Occitanie, Université de Toulouse, 31432 Toulouse, France
5
Centre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, Faculté de Médecine de Nantes, 44034 CEDEX 1 Nantes, France
6
Centre Hospitalier Universitaire de Nantes, Service de Chirurgie Orthopédique, Faculté de Médecine de Nantes, Université de Nantes, 44034 CEDEX 1 Nantes, France
7
Centre Hospitalier Régional Universitaire de Tours, Service d’Hématologie Biologique, 37044 CEDEX 9 Tours, France
8
National Center for Scientific Research (CNRS) GDR 3697, 75020 Paris, France
9
National Center for Scientific Research (CNRS) ERL 7001 LNOx, 37032 CEDEX 1 Tours, Université de Tours, 37044 Tours, France
10
Centre Hospitalier Régional Universitaire de Tours, Hôpital Trousseau, Service d’Anatomie Pathologique, Faculté de Médecine de Tours, Université de Tours, 37044 CEDEX 9 Tours, France
*
Author to whom correspondence should be addressed.
Received: 31 January 2018 / Revised: 10 February 2018 / Accepted: 12 February 2018 / Published: 1 March 2018
(This article belongs to the Special Issue Current Advances in Soft Tissue and Bone Sarcoma)
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Abstract

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments. View Full-Text
Keywords: osteosarcoma; mesenchymal stem cells; cancer stem cells; spheres osteosarcoma; mesenchymal stem cells; cancer stem cells; spheres
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Le Nail, L.-R.; Brennan, M.; Rosset, P.; Deschaseaux, F.; Piloquet, P.; Pichon, O.; Le Caignec, C.; Crenn, V.; Layrolle, P.; Hérault, O.; De Pinieux, G.; Trichet, V. Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma. Int. J. Mol. Sci. 2018, 19, 707.

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