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Osteosarcoma Development and Stem Cell Differentiation

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Osteosarcoma is the most common nonhematologic malignancy of bone in children and adults. The peak incidence occurs in the second decade of life, with a smaller peak after age 50. Osteosarcoma typically arises around the growth plate of long bones. Most osteosarcoma tumors are of high grade and tend to develop pulmonary metastases. Despite clinical improvements, patients with metastatic or recurrent diseases have a poor prognosis. Here, we reviewed the current understanding of human osteosarcoma, with an emphasis on potential links between defective osteogenic differentiation and bone tumorigenesis. Existing data indicate osteosarcoma tumors display a broad range of genetic and molecular alterations, including the gains, losses, or arrangements of chromosomal regions, inactivation of tumor suppressor genes, and the deregulation of major signaling pathways. However, except for p53 and/or RB mutations, most alterations are not constantly detected in the majority of osteosarcoma tumors. With a rapid expansion of our knowledge about stem cell biology, emerging evidence suggests osteosarcoma should be regarded as a differentiation disease caused by genetic and epigenetic changes that interrupt osteoblast differentiation from mesenchymal stem cells. Understanding the molecular pathogenesis of human osteosarcoma could ultimately lead to the development of diagnostic and prognostic markers, as well as targeted therapeutics for osteosarcoma patients.

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Acknowledgments

We apologize to the investigators whose original work could not be cited due to space constraints.

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Authors and Affiliations

  1. The Second Affiliated Hospital and the Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education, Chongqing Medical University, Chongqing, China

    Ni Tang MD, PhD, Jinyong Luo MD & Tong-Chuan He MD, PhD

  2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC 3079, Chicago, IL, 60637, USA

    Ni Tang MD, PhD, Wen-Xin Song MD, Jinyong Luo MD, Rex C. Haydon MD, PhD & Tong-Chuan He MD, PhD

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  1. Ni Tang MD, PhD
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One or more of the authors have received funding from the American Cancer Society (TCH), The Brinson Foundation (RCH, TCH), the Orthopaedic Research and Education Foundation (RCH), and the National Institutes of Health (RCH, TCH).

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Tang, N., Song, WX., Luo, J. et al. Osteosarcoma Development and Stem Cell Differentiation. Clin Orthop Relat Res 466, 2114–2130 (2008). https://doi.org/10.1007/s11999-008-0335-z

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