Bone and hematological regulation by their modulators

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: MIYAMOTO Kana 慶應義塾大学, 医学部, 研究員 (60464997)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 腫瘍 / 骨代謝 / 腫瘍医学

Outline of Final Research Achievements

We found that tumor necrosis factor alpha (TNFα) is required for tumorigenesis of an osteosarcoma cell line, AX cells. AX cells were generated by transducing c-Myc oncogene into Ink4a-deficient mesenchymal stem cells. Transplantation of AX cells into wild-type mouse peritoneal cavity resulted in tumorigenesis leading to mortality within 21 days. We found that TNFα-expressing macrophages were recruited to tumor lesions, and lethal tumor development was not observed in TNFα-deficient mice, suggesting that TNFα is required for tumorigenesis of AX cells. Osteoblastic gene expression was significantly inhibited in AX cells by TNFα, and such inhibition was reversed by addition of either a TNFα-inhibitor or a MEK thereby ERK inhibitor. These results suggest that the undifferentiated state of AX cells was the TNFα-ERK pathway dependent.

Free Research Field

血液内科学