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Clinical & Experimental Metastasis

, Volume 32, Issue 6, pp 579–591 | Cite as

Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone

  • Mihoko Hatano
  • Yoshihiro MatsumotoEmail author
  • Jun-ichi Fukushi
  • Tomoya Matsunobu
  • Makoto Endo
  • Seiji Okada
  • Kunio Iura
  • Satoshi Kamura
  • Toshifumi Fujiwara
  • Keiichiro Iida
  • Yuko Fujiwara
  • Akira Nabeshima
  • Nobuhiko Yokoyama
  • Suguru Fukushima
  • Yoshinao Oda
  • Yukihide Iwamoto
Research Paper

Abstract

Ewing sarcoma (ES) is a small round-cell tumor of the bones and soft tissues. ES frequently causes distant metastases, particularly in the lung and bone, which worsens patient prognosis. Cadherin-11 (Cad-11) is an adhesion molecule that is highly expressed in osteoblasts. Its expression is associated with bone metastases in prostate and breast cancer patients, and is known to occur in ES. Here we investigated the effects of Cad-11 on bone metastases of ES. Human ES cell lines RD-ES, SK-ES-1, SK-N-MC, and TC-71 cells were transduced with lentivirus containing Cad-11 shRNA or control shRNA (ES/Cad-11 and ES/Ctr). RD-ES and TC-71 were infected with a lentivirus luciferase vector. Adhesion assays were performed using these cells and recombinant Cad-11-Fc chimera or mouse osteoblast cell line MC3T3-E1. Cell motility was investigated via wound-healing assay. Intracardiac injection of RD-ES/Cad-11 and RD-ES/Ctr was used to create a mouse model of experimental bone metastasis. The association between Cad-11 expression and bone metastases and clinical prognosis in ES patients was analyzed by immunohistochemistry. We found knockdown of Cad-11 in ES cells resulted in reduced attachment ability and cell motility. In a mouse model of metastasis, RD-ES/Cad-11 cells caused fewer metastases than RD-ES/Ctr cells. The expression of Cad-11 in ES patients was significantly related to bone metastases (P < 0.05, logistic regression) and poorer overall survival (P < 0.05, log-rank test). These findings may explain that Cad-11 in ES cells may be essential for cell adhesion and motility, and is a promising molecular target for patients with ES.

Keywords

Ewing sarcoma Cadherin-11 Bone metastasis Osteoblasts Adhesion molecule Chemokinesis 

Abbreviations

ES

Ewing sarcoma

Cad-11

Cadherin-11

Ctr

Control

SD

Standard deviation

MMP

Matrix metalloproteinase

FACS

Fluorescence activated cell sorting

Notes

Acknowledgments

We thank Dr. Junji Kishimoto for the helpful suggestions on statistics. This work was supported by a Grant-in-Aid for Scientific Research (25293325) from the Japan Society for the Promotion of Science (Y. Iwamoto), and a Grant-in-Aid for Clinical Research Evidence-Based Medicine and Cancer Research from the Ministry of Health, Labor and Welfare of Japan (Y. Iwamoto).

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

Supplementary material

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Supplementary material 1 (DOCX 25 kb)
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Supplementary material 8 (PDF 90 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Mihoko Hatano
    • 1
  • Yoshihiro Matsumoto
    • 1
    Email author
  • Jun-ichi Fukushi
    • 1
  • Tomoya Matsunobu
    • 1
  • Makoto Endo
    • 1
  • Seiji Okada
    • 1
    • 2
  • Kunio Iura
    • 3
  • Satoshi Kamura
    • 1
  • Toshifumi Fujiwara
    • 1
  • Keiichiro Iida
    • 1
  • Yuko Fujiwara
    • 1
  • Akira Nabeshima
    • 1
  • Nobuhiko Yokoyama
    • 1
  • Suguru Fukushima
    • 1
  • Yoshinao Oda
    • 3
  • Yukihide Iwamoto
    • 1
  1. 1.Department of Orthopaedic Surgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Advanced Medical Initiatives, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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