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

Mihoko Hatano, Yoshihiro Matsumoto, 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 output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)579-591
Number of pages13
JournalClinical and Experimental Metastasis
Volume32
Issue number6
DOIs
Publication statusPublished - Aug 25 2015

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Ewing's Sarcoma
Neoplasm Metastasis
Bone and Bones
osteoblast cadherin
Cell Movement
Lentivirus
Osteoblasts
Small Interfering RNA
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone. / Hatano, Mihoko; Matsumoto, Yoshihiro; Fukushi, Jun ichi; Matsunobu, Tomoya; Endo, Makoto; Okada, Seiji; Iura, Kunio; Kamura, Satoshi; Fujiwara, Toshifumi; Iida, Keiichiro; Fujiwara, Yuko; Nabeshima, Akira; Yokoyama, Nobuhiko; Fukushima, Suguru; Oda, Yoshinao; Iwamoto, Yukihide.

In: Clinical and Experimental Metastasis, Vol. 32, No. 6, 25.08.2015, p. 579-591.

Research output: Contribution to journalArticle

Hatano, M, Matsumoto, Y, Fukushi, JI, Matsunobu, T, Endo, M, Okada, S, Iura, K, Kamura, S, Fujiwara, T, Iida, K, Fujiwara, Y, Nabeshima, A, Yokoyama, N, Fukushima, S, Oda, Y & Iwamoto, Y 2015, 'Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone', Clinical and Experimental Metastasis, vol. 32, no. 6, pp. 579-591. https://doi.org/10.1007/s10585-015-9729-y
Hatano, Mihoko ; Matsumoto, Yoshihiro ; Fukushi, Jun ichi ; Matsunobu, Tomoya ; Endo, Makoto ; Okada, Seiji ; Iura, Kunio ; Kamura, Satoshi ; Fujiwara, Toshifumi ; Iida, Keiichiro ; Fujiwara, Yuko ; Nabeshima, Akira ; Yokoyama, Nobuhiko ; Fukushima, Suguru ; Oda, Yoshinao ; Iwamoto, Yukihide. / Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone. In: Clinical and Experimental Metastasis. 2015 ; Vol. 32, No. 6. pp. 579-591.
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AU - Hatano, Mihoko

AU - Matsumoto, Yoshihiro

AU - Fukushi, Jun ichi

AU - Matsunobu, Tomoya

AU - Endo, Makoto

AU - Okada, Seiji

AU - Iura, Kunio

AU - Kamura, Satoshi

AU - Fujiwara, Toshifumi

AU - Iida, Keiichiro

AU - Fujiwara, Yuko

AU - Nabeshima, Akira

AU - Yokoyama, Nobuhiko

AU - Fukushima, Suguru

AU - Oda, Yoshinao

AU - Iwamoto, Yukihide

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N2 - 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.

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