TY - JOUR
T1 - Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone
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
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media Dordrecht.
PY - 2015/8/25
Y1 - 2015/8/25
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.
AB - 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.
KW - Adhesion molecule
KW - Bone metastasis
KW - Cadherin-11
KW - Chemokinesis
KW - Ewing sarcoma
KW - Osteoblasts
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U2 - 10.1007/s10585-015-9729-y
DO - 10.1007/s10585-015-9729-y
M3 - Article
C2 - 26092671
AN - SCOPUS:84937968268
SN - 0262-0898
VL - 32
SP - 579
EP - 591
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 6
ER -
