RRC ID 37516
著者 Hatano M, Matsumoto Y, Fukushi J, 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.
タイトル Cadherin-11 regulates the metastasis of Ewing sarcoma cells to bone.
ジャーナル Clin Exp Metastasis
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.
巻・号 32(6)
ページ 579-91
公開日 2015-8-1
DOI 10.1007/s10585-015-9729-y
PMID 26092671
MeSH Animals Antibodies, Monoclonal / pharmacology* Apoptosis Blotting, Western Bone Neoplasms / metabolism Bone Neoplasms / mortality Bone Neoplasms / secondary* Cadherins / antagonists & inhibitors Cadherins / immunology Cadherins / metabolism* Cell Adhesion Cell Movement* Cell Proliferation Coculture Techniques Female Flow Cytometry Humans Immunoenzyme Techniques Luciferases / metabolism Mice Mice, Inbred BALB C Mice, Nude Neoplasm Staging Osteoblasts / metabolism Osteoblasts / pathology* Prognosis RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Sarcoma, Ewing / metabolism Sarcoma, Ewing / mortality Sarcoma, Ewing / pathology* Survival Rate Tumor Cells, Cultured Wound Healing Xenograft Model Antitumor Assays
IF 3.027
引用数 11
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)