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Yang Y, Yang R, Roth M, et al. Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model. Genes Cancer. 2017;8(1):484-494doi: 10.18632/genesandcancer.133.
Yang, Y., Yang, R., Roth, M., Piperdi, S., Zhang, W., Dorfman, H., Rao, P., Park, A., Tripathi, S., Freeman, C., Zhang, Y., Sowers, R., Rosenblum, J., Geller, D., Hoang, B., Gill, J., & Gorlick, R. (2017). Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model. Genes & cancer, 8(1), 484-494. https://doi.org/10.18632/genesandcancer.133
Yang, Yi, et al. "Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model." Genes & cancer vol. 8,1 (2017): 484-494. doi: https://doi.org/10.18632/genesandcancer.133
Yang Y, Yang R, Roth M, Piperdi S, Zhang W, Dorfman H, Rao P, Park A, Tripathi S, Freeman C, Zhang Y, Sowers R, Rosenblum J, Geller D, Hoang B, Gill J, Gorlick R. Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model. Genes Cancer. 2017 Jan;8(1):484-494. doi: 10.18632/genesandcancer.133. PMID: 28435520; PMCID: PMC5396624.
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Genes Cancer. 2017 Jan;8(1):484-494. doi: 10.18632/genesandcancer.133.

Genetically transforming human osteoblasts to sarcoma: development of an osteosarcoma model.

Genes & cancer

Yi Yang, Rui Yang, Michael Roth, Sajida Piperdi, Wendong Zhang, Howard Dorfman, Pulivarthi Rao, Amy Park, Sandeep Tripathi, Carrie Freeman, Yunjia Zhang, Rebecca Sowers, Jeremy Rosenblum, David Geller, Bang Hoang, Jonathan Gill, Richard Gorlick

Affiliations

  1. Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
  2. Current affiliations: Department of Orthopaedic Surgery, Musculoskeletal Tumor Center, People's Hospital, Peking University, Beijing, China.
  3. Department of Orthopaedic Surgery, Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, Bronx, NY, USA.
  4. Department of Pathology, Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, Bronx, NY, USA.
  5. Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
  6. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
  7. Current affiliations: Pediatrics Administration, The University of Texas MD Anderson Cancer Center, Children's Cancer Hospital, Houston, TX, USA.

PMID: 28435520 PMCID: PMC5396624 DOI: 10.18632/genesandcancer.133

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

Keywords: mesenchymal stem cells; osteoblast; osteosarcoma

Conflict of interest statement

CONFLICTS OF INTEREST The authors confirm that there are no conflicts of interest.

References

  1. Cell Res. 2012 Jan;22(1):62-77 - PubMed
  2. J Pathol. 2009 Nov;219(3):294-305 - PubMed
  3. Cancer Res. 2001 May 1;61(9):3556-60 - PubMed
  4. Cytogenet Genome Res. 2008;122(1):5-15 - PubMed
  5. Stem Cells. 2011 Mar;29(3):397-403 - PubMed
  6. Neoplasia. 2009 Apr;11(4):397-407 - PubMed
  7. J Bone Miner Res. 2010 Apr;25(4):683-91 - PubMed
  8. Oncogene. 2013 Oct 10;32(41):4970-80 - PubMed
  9. Stem Cells Dev. 2010 Aug;19(8):1167-73 - PubMed
  10. Cancer. 1987 Jan 15;59(2):324-8 - PubMed
  11. Oncogene. 2006 Dec 14;25(59):7673-9 - PubMed
  12. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11851-6 - PubMed
  13. Nat Med. 2007 Aug;13(8):992-7 - PubMed
  14. Cancer Res. 2007 Oct 1;67(19):9142-9 - PubMed
  15. Cancer. 2009 Apr 1;115(7):1531-43 - PubMed
  16. Cancer Res. 2005 Jun 1;65(11):4490-5 - PubMed
  17. Cancer Res. 2004 Mar 1;64(5):1655-63 - PubMed
  18. Clin Sarcoma Res. 2013 Jul 23;3(1):10 - PubMed
  19. Cancer Genet Cytogenet. 1994 Oct;77(1):81-8 - PubMed
  20. Am J Pathol. 2002 Aug;161(2):365-71 - PubMed
  21. Stem Cells. 2007 Feb;25(2):371-9 - PubMed
  22. Genes Dev. 2008 Jun 15;22(12):1662-76 - PubMed
  23. Hum Pathol. 1991 Jun;22(6):583-90 - PubMed
  24. Sarcoma. 2012;2012:164803 - PubMed
  25. Stem Cells. 2014 May;32(5):1136-48 - PubMed
  26. Bioinformatics. 2004 Feb 12;20(3):307-15 - PubMed
  27. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6223-8 - PubMed
  28. Cancer Res. 2007 Nov 15;67(22):10889-98 - PubMed
  29. Nature. 1999 Jul 29;400(6743):464-8 - PubMed
  30. Pharmacol Ther. 2013 Jan;137(1):89-99 - PubMed
  31. Cancer Res. 2001 Jul 1;61(13):4956-60 - PubMed
  32. Biochem Biophys Res Commun. 2007 Feb 2;353(1):60-6 - PubMed
  33. Lab Invest. 2011 Aug;91(8):1195-205 - PubMed
  34. Carcinogenesis. 2009 Oct;30(10):1789-95 - PubMed
  35. Clin Adv Hematol Oncol. 2010 Oct;8(10):705-18 - PubMed
  36. Stem Cells. 2006 Apr;24(4):1095-103 - PubMed
  37. Cancer. 2009 Oct 15;115(20):4795-806 - PubMed
  38. J Cell Biochem. 2014 Aug;115(8):1420-9 - PubMed
  39. Bone. 2014 May;62:56-63 - PubMed

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