title: A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties.
abstract: Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo.
authors.affiliation: Department of Cell Therapy, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Norway. Electronic address: j.m.nestvold@medisin.uio.no.
authors.forename: Janne
authors.initials: J
authors.lastname: Nestvold
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Rekdal
authors.affiliation: Department of Cell Therapy, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fodstad
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005354:Fibrosarcoma / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology*; D051381:Rats; D011923:Rats, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
keywords: Cancer stem cells; Fibrosarcoma tumor model; Mesenchymal stem cells; Side population; Transformed cell line