title: Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone.
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.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Hatano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Fukushi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsunobu
authors.forename: Makoto
authors.initials: M
authors.lastname: Endo
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Kunio
authors.initials: K
authors.lastname: Iura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Iida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Akira
authors.initials: A
authors.lastname: Nabeshima
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Suguru
authors.initials: S
authors.lastname: Fukushima
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D015820:Cadherins; D012333:RNA, Messenger; C086960:osteoblast cadherin; D008156:Luciferases