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S100A6 Expression and Function in Human Osteosarcoma

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

Abstract

There is a critical need to identify markers that can accurately identify existing or predict future metastatic disease in patients with osteosarcoma since the majority of patients present with undetectable micrometastatic disease. We previously reported S100A6 is overexpressed in human osteosarcoma and increased expression of S100A6 by immunohistochemistry correlated with decreased clinical metastasis. We have established 11 primary cultures from biopsies of patients with osteosarcoma and ten of the 11 primary cultures have increased expression of S100A6 relative to normal human osteoblasts. To further explore possible mechanisms for metastasis suppression previously reported, we used in this report siRNA-mediated knockdown of S100A6 in four commonly used human osteosarcoma lines, then examined their cell adhesion, migration, and invasion properties. Knockdown of S100A6 expression inhibited cell adhesion and promoted cell migration and invasion in these lines. Conversely, S100A6 overexpression enhanced cell adhesion and inhibited cell invasion. Our data demonstrate S100A6 is commonly overexpressed in human osteosarcoma. S100A6 may inhibit osteosarcoma metastasis by promoting cell adhesion and inhibiting cell motility and invasion. Thus, S100A6 may be considered a potential marker for human osteosarcoma with prognostic value for identifying patients without metastases.

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Acknowledgments

We thank Drs. Michael A. Simon, Terrance D. Peabody, and Rex C. Haydon for supplying the patient samples. We also would like to thank Dezhang Huo from The University of Chicago Health Studies Department for assistance with the statistical analysis.

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Correspondence to Hue H. Luu MD.

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One or more of the authors (HHL, TCH) have received funding from the Orthopaedic Research and Education Foundation, the Brinson Foundation, and the American Cancer Society (ACS-IRG).

Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Luo, X., Sharff, K.A., Chen, J. et al. S100A6 Expression and Function in Human Osteosarcoma. Clin Orthop Relat Res 466, 2060–2070 (2008). https://doi.org/10.1007/s11999-008-0361-x

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  • DOI: https://doi.org/10.1007/s11999-008-0361-x

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