title: Mesenchymal stromal cells from primary osteosarcoma are non-malignant and strikingly similar to their bone marrow counterparts.
abstract: 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 10(5) 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 10(5) 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.
authors.affiliation: Lund Stem Cell Center, University of Lund, Lund, Sweden.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Brune
authors.forename: Ariane
authors.initials: A
authors.lastname: Tormin
authors.forename: Maria C
authors.initials: MC
authors.lastname: Johansson
authors.forename: Pehr
authors.initials: P
authors.lastname: Rissler
authors.forename: Otte
authors.initials: O
authors.lastname: Brosjö
authors.forename: Richard
authors.initials: R
authors.lastname: Löfvenberg
authors.forename: Fredrik Vult
authors.initials: FV
authors.lastname: von Steyern
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Anders
authors.initials: A
authors.lastname: Rydholm
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
mesh_terms: D000293:Adolescent; D001854:Bone Marrow Cells / Q000166:cytology*; D001859:Bone Neoplasms / Q000473:pathology*; D018929:Cell Culture Techniques; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D039902:Multipotent Stem Cells; D012516:Osteosarcoma / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology; D059016:Tumor Microenvironment; D055815:Young Adult