Mesenchymal stromal cells from primary osteosarcoma are non-malignant and strikingly similar to their bone marrow counterparts
Jan C. Brune
Lund Stem Cell Center, University of Lund, Lund, Sweden
Search for more papers by this authorAriane Tormin
Lund Stem Cell Center, University of Lund, Lund, Sweden
Search for more papers by this authorMaria C. Johansson
Department of Oncology, Lund University Hospital, Lund, Sweden
Search for more papers by this authorPehr Rissler
Department of Pathology, Lund University Hospital, Lund, Sweden
Search for more papers by this authorOtte Brosjö
Department of Orthopedics, Karolinska Hospital, Stockholm, Sweden
Search for more papers by this authorRichard Löfvenberg
Department of Orthopedics, Umeå University Hospital, Umeå, Sweden
Search for more papers by this authorFredrik Vult von Steyern
Department of Orthopedics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorFredrik Mertens
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorAnders Rydholm
Department of Orthopedics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorCorresponding Author
Stefan Scheding
Lund Stem Cell Center, University of Lund, Lund, Sweden
Department of Hematology, Lund University Hospital, Lund, Sweden
Tel: +46 46 222 3331, Fax: +46 46 222 3600
Lund Stem Cell Center, BMC-B10, Klinikgatan 26, S-22184 Lund, SwedenSearch for more papers by this authorJan C. Brune
Lund Stem Cell Center, University of Lund, Lund, Sweden
Search for more papers by this authorAriane Tormin
Lund Stem Cell Center, University of Lund, Lund, Sweden
Search for more papers by this authorMaria C. Johansson
Department of Oncology, Lund University Hospital, Lund, Sweden
Search for more papers by this authorPehr Rissler
Department of Pathology, Lund University Hospital, Lund, Sweden
Search for more papers by this authorOtte Brosjö
Department of Orthopedics, Karolinska Hospital, Stockholm, Sweden
Search for more papers by this authorRichard Löfvenberg
Department of Orthopedics, Umeå University Hospital, Umeå, Sweden
Search for more papers by this authorFredrik Vult von Steyern
Department of Orthopedics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorFredrik Mertens
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorAnders Rydholm
Department of Orthopedics, Lund University Hospital, Lund, Sweden
Search for more papers by this authorCorresponding Author
Stefan Scheding
Lund Stem Cell Center, University of Lund, Lund, Sweden
Department of Hematology, Lund University Hospital, Lund, Sweden
Tel: +46 46 222 3331, Fax: +46 46 222 3600
Lund Stem Cell Center, BMC-B10, Klinikgatan 26, S-22184 Lund, SwedenSearch for more papers by this authorAbstract
Mesenchymal stromal cells (MSC) are multipotent cells that can be isolated from a number of human tissues. In cancer, MSC have been implicated with tumor growth, invasion, metastasis, drug resistance and were even suggested as possible tumor-initiating cells in osteosarcoma (OS). However, MSC from OS and their possible tumor origin have not yet been thoroughly investigated. Therefore, primary OS mesenchymal progenitors and OS-derived MSC were studied. OS samples contained very high frequencies of mesenchymal progenitor cells as measured by the colony-forming unit fibroblast (CFU-F) assay (median: 1,117 colonies per 105 cells, range: 133–3,000, n = 6). This is considerably higher compared to other human tissues such as normal bone marrow (BM) (1.3 ± 0.2 colonies per 105 cells, n = 8). OS-derived MSC (OS-MSC) showed normal MSC morphology and expressed the typical MSC surface marker profile (CD105/CD73/CD90/CD44/HLA-classI/CD166 positive, CD45/CD34/CD14/CD19/HLA-DR/CD31 negative). Furthermore, all OS-MSC samples could be differentiated into the osteogenic lineage, and all but one sample into adipocytes and chondrocytes. Genetic analysis of OS-MSC as well as OS-derived spheres showed no tumor-related chromosomal aberrations. OS-MSC expression of markers related to tumor-associated fibroblasts (fibroblast surface protein, alpha-smooth muscle actin, vimentin) was comparable to BM-MSC and OS-MSC growth was considerably affected by tyrosine kinase inhibitors. Taken together, our results demonstrate that normal, non-malignant mesenchymal stroma cells are isolated from OS when MSC culture techniques are applied. OS-MSC represent a major constituent of the tumor microenvironment, and they share many properties with BM-derived MSC.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IJC_25697_sm_suppfig1.tif2.6 MB | Supporting Figure 1. |
| IJC_25697_sm_suppfig2.tif6.6 MB | Supporting Figure 2. |
| IJC_25697_sm_suppfig3.tif18.8 MB | Supporting Figure 3. |
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