Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

Autocrine motility factor (AMF) plays an important role in the development of metastasis by regulating tumor cell motility. The expression of A M F 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 degrees C for 24 h. According to microarray results, HS1390, HSP70 and HSP27 expression was upregulatcd in osteosarcoma cells under hyperthermia. The intracellular, secreted A M F, m RNA of A M F and cell motility were evaluated by western blotting, HASA, RT-PCR, wound healing and phagokinetic track assays, respectively. The protein secretion and m RNA levels of AM F and tumor cell motility were significantly decreased by hyperthermia. Of note, the downrcgulated A M F 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 A M F expression and motility downregulated by hyperthermia. In conclusion, hyperthermia reduced AM F expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment.