The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation
Open accessAbstract
BACKGROUND: We previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC). METHODOLOGY/PRINCIPAL FINDINGS: Here we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection. CONCLUSIONS/SIGNIFICANCE: In our model, the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels. The cells then bypass cell crisis with acquisition of telomerase activity, Ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell.
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Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 1×
“Telomerase activity has been found in almost all human tumors but not in adjacent normal cells [21] and maintenance of telomere stability is required for the long-term proliferation of tumor cells [22].”
BackgroundCell-cycle checkpoints and cancer
Kastan, M. B., & Bartek, J. (2004) · Nature · doi:10.1038/nature03097 · Cited by 2,836
The RB and p53 pathways in cancer
Sherr, C. J., & McCormick, F. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00102-2 · Cited by 1,690
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Rules for Making Human Tumor Cells
Hahn, W. C., & Weinberg, R. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmra021902 · Cited by 951
Yeh, E., Cunningham, M., Arnold, H., Chasse, D., Monteith, T., Ivaldi, G., Hahn, W. C., Stukenberg, P. T., Shenolikar, S., Uchida, T., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1110 · Cited by 791
INK4a/ARF: A multifunctional tumor suppressor locus
Sharpless, N. E. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.08.021 · Cited by 442 · cited 2×
“The results suggest that p16 inhibition is essential for TMC generation, as is the case for human malignancies including glioblastoma, melanoma, pancreatic adenocarcinoma, non-small cell lung cancer, bladder carcinoma and oropharyngeal cancer, where this tumor suppressor is frequently lost [33].”
BackgroundAdult human mesenchymal stem cell as a target for neoplastic transformation
Serakinci, N., Guldberg, P., Burns, J. S., Abdallah, B., Schrødder, H., Jensen, T., & Kassem, M. (2004) · Oncogene · doi:10.1038/sj.onc.1207651 · Cited by 350
Coordinated regulation of life and death by RB
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Cited by
Mesenchymal Stromal Cells: Current Understanding and Clinical Status
Salem, H. K., & Thiemermann, C. (2010) · Stem Cells · doi:10.1002/stem.269 · Cited by 915
Stem Cells and Cell Therapies in Lung Biology and Lung Diseases
Weiss, D. J., Kolls, J. K., Ortiz, L. A., Panoskaltsis-Mortari, A., & Prockop, D. J. (2008) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200804-037dw · Cited by 309
Potential implications of mesenchymal stem cells in cancer therapy
Dai, L.-J., Moniri, M. R., Zeng, Z.-R., Zhou, J. X., Rayat, J., & Warnock, G. L. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.02.012 · Cited by 99
Quality of cell products: authenticity, identity, genomic stability and status of differentiation
Dittmar, K. E. J., Simann, M., Zghoul, N., Schön, O., Meyring, W., Hannig, H., Macke, L., Dirks, W. G., Miller, K., Garritsen, H. S. P., et al. (2010) · Transfusion Medicine and Hemotherapy · doi:10.1159/000284401 · Cited by 24
Metadata
- Authors
- Rubio, D., Garcia, S., Paz, M. F., De la Cueva, T., Lopez-Fernandez, L. A., Lloyd, A. C., Garcia-Castro, J., & Bernad, A.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-01-02
- Volume
- 3
- Issue
- 1
- Pages
- e1398
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2017945589
- Cited by
- 161
- References
- 9
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- gold
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- Rubio, D., Garcia, S., Paz, M. F., De la Cueva, T., Lopez-Fernandez, L. A., Lloyd, A. C., Garcia-Castro, J., & Bernad, A. (2008). Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation. PLoS ONE. https://doi.org/10.1371/journal.pone.0001398
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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