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Therapeutic potential of antibodies against FZD10, a cell-surface protein, for synovial sarcomas

Oncogene volume 24, pages 6201–6212 (2005)Cite this article

Abstract

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD10 decreased the amount of its product and suppressed growth of SS cells. Moreover, a polyclonal antibody specifically recognizing the extracellular domain (ECD) of FZD10 was markedly effective in mediating ADCC against FZD10-overexpressing synovial sarcoma cells in vitro. Injection of the antibody into SS xenografts in nude mice attenuated tumor growth, and TUNEL assays revealed clusters of apoptotic cells in antibody-treated xenografts. Taken together, these findings suggest that a humanized antibody against FZD10 might be a promising treatment for patients with tumors that overexpress FZD10; minimal or no adverse reactions would be expected because FZD10 protein is not abundant in vital organs.

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Abbreviations

SS:

synovial sarcoma

FZD10:

frizzled homologue 10

siRNA:

small-interfering RNA

ADCC:

antibody-dependent cell-mediated cytotoxicity

ECD:

extracellular domain

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Acknowledgements

We gratefully thank Ms Kie Naito and Ms Kyoko Kijima for technical assistance; Drs Hiroshi Sonobe and Akira Kawai for kindly providing SS cell lines; and Dr Kazuhisa Ohgaki for preparing tumor samples. This work was supported in part by Research for the Future Program Grant #00L01402 from the Japan Society for the Promotion of Science.

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Author notes

  1. Satoshi Nagayama and Chikako Fukukawa: These authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Satoshi Nagayama, Chikako Fukukawa, Toyomasa Katagiri & Yusuke Nakamura

  2. Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Satoshi Nagayama & Masayuki Imamura

  3. Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan

    Takeshi Okamoto, Tomoki Aoyama & Junya Toguchida

  4. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Takeshi Okamoto & Tomoki Aoyama

  5. Department of Laboratory Medicine, Division of Pathology, Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Naoki Oyaizu

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  1. Satoshi Nagayama
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Correspondence to Yusuke Nakamura.

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Nagayama, S., Fukukawa, C., Katagiri, T. et al. Therapeutic potential of antibodies against FZD10, a cell-surface protein, for synovial sarcomas. Oncogene 24, 6201–6212 (2005). https://doi.org/10.1038/sj.onc.1208780

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