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mTOR Signal Transduction Pathways Contribute to TN-C FNIII A1 Overexpression by Mechanical Stress in Osteosarcoma Cells

  • Zheng, Lianhe (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University) ;
  • Zhang, Dianzhong (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University) ;
  • Zhang, Yunfei (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University) ;
  • Wen, Yanhua (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University) ;
  • Wang, Yucai (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
  • Received : 2013.09.05
  • Accepted : 2014.01.14
  • Published : 2014.02.28

Abstract

Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosarcoma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migration. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients.

Keywords

References

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