title: Bone marrow-derived mesenchymal stem cells undergo JCV T-antigen mediated transformation and generate tumors with neuroectodermal characteristics.
abstract: There is now accumulating evidence showing that some tumors may arise from transformed stem cells. In this study we demonstrate that adult bone marrow- derived mesenchymal stem cells (MSCs) undergo neoplastic transformation induced by the human polyomavirus JCV, early protein, T-antigen, and are tumorigenic when transplanted into the flanks of Nude mice as compared to non-transformed MSCs. Histologically, the tumors are heterogeneous with mesenchymal and neural crest characteristics as evidenced by expression of the neural crest markers p75, SOX-10, and S-100, with populations of tumor cells exhibiting characteristics of primitive neuroectodermal cells. In addition, a subset of T-antigen positive tumor cells exhibit a high proliferation index as detected by Ki-67 labeling, and co-express CD133, a marker which is expressed on cancer stem cells. These results show that tumors with neuroectodermal characteristics may arise from transformation of MSCs, a globally accessible adult stem cell with multipotent differentiation capacity. In light of earlier reports on the association of JCV with a broad variety of human tumors, our data suggests that T-antigen transformation of adult stem cells with a multipotent capacity can serve as a possible common origin for some of these cancers, and offers a novel model for oncogenesis.
authors.affiliation: Departments of Neuroscience and Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Sergio
authors.initials: S
authors.lastname: Piña-Oviedo
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Georgina
authors.initials: G
authors.lastname: Perez-Liz
authors.affiliation: Department of Neurology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Augelli
authors.affiliation: Department of Neurology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: S Ausim
authors.initials: SA
authors.lastname: Azizi
authors.affiliation: Temple University School of Medicine; Philadelphia, PA.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Department of Neurology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Barbara
authors.initials: B
authors.lastname: Krynska
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007577:JC Virus / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017599:Neuroectodermal Tumors / Q000378:metabolism / Q000473:pathology*; D051381:Rats
chemical_list: D000957:Antigens, Viral, Tumor