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Roles of bone morphogenetic protein signaling in osteosarcoma

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Abstract

Purpose

Since the original extraction of bone morphogenetic proteins (BMPs) from bovine bone, research interest and clinical use has increased exponentially. With this, a concomitant analysis of BMP expression in bone tumours has been performed. BMP ligands, receptors, and signaling activity have been observed in diverse benign and malignant bone tumours. However, the reported expression, function, and importance of BMPs in bone tumours, and specifically osteosarcomas, have been far from uniform. This review highlights recent advances in understanding the role of BMP signaling in osteosarcoma biology, focusing on the sometimes divergent findings by various researchers and the challenges inherent in the study of osteosarcoma.

Methods

We performed a literature review of all studies examining BMP signaling in osteosarcoma.

Results

Overall, multiple BMP ligands and receptors are expressed in most osteosarcoma cell lines and subtypes, although BMP signaling may be reduced in comparison with benign bone-forming tumours. Studies suggest that osteosarcomas with different lineages of differentiation may have differential expression of BMP ligands. Although significant disagreement in the literature exists, the presence of BMP signaling in osteosarcoma may impart a worse prognosis. On the cellular level, BMP signaling appears to mediate promigratory effects in osteosarcoma and chondrosarcoma cell types, possibly via interaction and activation of Integrin β1.

Conclusions

BMP signaling has clear biologic importance in osteosarcoma, although it is not yet fully understood. Future questions for study include assessing the utility of BMP signaling in prognostication of osteosarcoma and the potential modulation of BMP signaling for inhibition of osteosarcomagenesis, growth and invasion.

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Acknowledgments

We thank A.S. James for his excellent technical assistance. AWJ was supported by the UCLA Pathology Translational Research Fund. Human specimens were obtained under University of California IRB # 13–000897.

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Authors and Affiliations

  1. Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, CHS A3-251, Los Angeles, CA, 90077, USA

    Alan Nguyen, Sarah M. Dry & Aaron W. James

  2. School of Dentistry, University of California, Los Angeles, CA, USA

    Alan Nguyen

  3. Division of Dentistry and Orthodontics, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Michelle A. Scott

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  1. Alan Nguyen
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  2. Michelle A. Scott
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  4. Aaron W. James
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Correspondence to Aaron W. James.

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Nguyen, A., Scott, M.A., Dry, S.M. et al. Roles of bone morphogenetic protein signaling in osteosarcoma. International Orthopaedics (SICOT) 38, 2313–2322 (2014). https://doi.org/10.1007/s00264-014-2512-x

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