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Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

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

Abstract

Inhibitors of specific tyrosine kinases are attractive lead compounds for development of targeted chemotherapies for many tumors, including osteosarcoma. We asked whether inhibition of specific tyrosine kinases would decrease the motility, colony formation, and/or invasiveness by human osteosarcoma cell lines (TE85, MNNG, 143B, SAOS-2, LM-7). An EGF-R inhibitor reduced motility of all five cell lines by 50% to 80%. In contrast, an IGF-1R inhibitor preferentially reduced motility by 42% in LM-7 cells and a met inhibitor preferentially reduced motility by 80% in MNNG cells. The inhibitors of EGF-R, IGF-1R, and met reduced colony formation by more than 80% in all tested cell lines (TE85, MNNG, 143B). The EGF-R inhibitor reduced invasiveness by 62% in 143B cells. The JAK inhibitor increased motility of SAOS-2 and LM7 cells without affecting colony formation or invasiveness. Inhibitors of HER-2, NGF-R, and PDGF-Rs did not affect motility, invasiveness, or colony formation. These results support the hypothesis that specific tyrosine kinases regulate tumorigenesis and/or metastasis in osteosarcoma.

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Acknowledgments

This paper is dedicated to the memory of John R. Carter, MD. We thank E. Kleinerman for providing the SAOS-2 and LM-7 cell lines, L. Licate and T. Egelhoff for advice on motility and invasion assays, H. Luu for advice on colony formation assays, and T. Matsushita for advice on microscopy.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Avenue, 6th Floor Hanna House, Cleveland, OH, 44118, USA

    Patrick J. Messerschmitt MD, Ashley N. Rettew BS, Robert E. Brookover BS, Ryan M. Garcia MD, Patrick J. Getty MD & Edward M. Greenfield PhD

  2. Department of Pathology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Ashley N. Rettew BS & Edward M. Greenfield PhD

  3. Department of Physiology & Biophysics, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Edward M. Greenfield PhD

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  1. Patrick J. Messerschmitt MD
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  2. Ashley N. Rettew BS
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  3. Robert E. Brookover BS
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  4. Ryan M. Garcia MD
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Correspondence to Patrick J. Messerschmitt MD.

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One of the authors (PJM) received funding through an Allen Research Fellowship; one of the authors (REB) received funding through a Silber Student Fellowship from the Ohio Division of the American Cancer Society.

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Messerschmitt, P.J., Rettew, A.N., Brookover, R.E. et al. Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro. Clin Orthop Relat Res 466, 2168–2175 (2008). https://doi.org/10.1007/s11999-008-0338-9

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