title: Hyperthermia reduces migration of osteosarcoma by suppression of autocrine             motility factor.
abstract: Autocrine motility factor (AMF) plays an important role in the development             of metastasis by regulating tumor cell motility. The expression of AMF is associated             with metastasis in malignant musculoskeletal tumors including osteosarcoma. Recent             studies indicated that hyperthermia contributes to the improvement of the prognosis             of patients with soft tissue sarcomas; however, few reports have evaluated the             impact of hyperthermia on tumor cell motility, which is an important factor of             metastasis. The purpose of this study was to evaluate the effect of hyperthermia             with or without heat shock protein (HSP) inhibitors on the motility and AMF expression             in an osteosarcoma cell line. Hyperthermia was carried out at 41˚C for 24 h. According             to microarray results, HSP90, HSP70 and HSP27 expression was upregulated in osteosarcoma             cells under hyperthermia. The intracellular, secreted AMF, mRNA of AMF and cell             motility were evaluated by western blotting, ELISA, RT-PCR, wound healing and             phagokinetic track assays, respectively. The protein secretion and mRNA levels             of AMF and tumor cell motility were significantly decreased by hyperthermia. Of             note, the downregulated AMF expression and motility were recovered by the addition             of an HSP27 inhibitor. By contrast, the HSP90 and HSP70/72/105 inhibitors had             no effect on AMF expression and motility downregulated by hyperthermia. In conclusion,             hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may             therefore be applied as osteosarcoma treatment.
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine,                     Gunma University, Maebashi, Gunma, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Nakajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Hideomi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagishi
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006361:Heating; D006801:Humans; D006979:Hyperthermia, Induced; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D005956:Glucose-6-Phosphate Isomerase