Genetically transforming human osteoblasts to sarcoma: Development of an osteosarcoma model

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

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)484-494
Number of pages11
JournalGenes and Cancer
Volume8
Issue number1-2
DOIs
StatePublished - Jan 2017

Keywords

  • Mesenchymal stem cells
  • Osteoblast
  • Osteosarcoma

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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    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 and Cancer, 8(1-2), 484-494. https://doi.org/10.18632/genesandcancer.133