Target gene screening of TGF-b signaling and functional analysis for differentiation-inducing therapy of chondrosarcoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kagoshima University
• Principal Investigator: Yokouchi Masahiro 鹿児島大学, 医歯学域医学系, 講師 (80359976)
• Co-Investigator(Kenkyū-buntansha): Maeda Shingo 鹿児島大学, 医歯(薬)学総合研究科, 特任准教授 (60353463) ; Komiya Setsuro 鹿児島大学, 医歯学域医学系, 教授 (30178371) ; Ishidou Yasuhiro 鹿児島大学, 医歯(薬)学総合研究科, 特任准教授 (10300740)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 軟骨肉腫 / 内軟骨腫 / TGF-b / 分化度

Outline of Final Research Achievements

It is one of the major dilemma for orthopaedic oncologists that, because histology of low grade chondrosarcoma and its benign counterpart enchondroma resembles, there are difficulties in distinguishing these two tumors. Our aim of this study was to discover molecular markers specific for each type of tumor. Moreover, we intended to understand underlying mechanism in lowered differentiation status of chondrosarcoma, to develop differentiation-initiating therapy. We focused on TGF-b signaling, because it is a crucial pathway in chondrocyte differentiation. By immunohistochemistry for phosphorylated SMAD2/3, the TGF-b signaling intracellular mediators, we found malignant grading-dependent increase of TGF-b signaling. We searched for genes which expression was altered by TGF-b in chondrosarcoma to find PEG10 to be down-regulated by the pathway. The combined expression analysis of p-SMAD2/3 and PEG10 may help distinguishing and diagnosing these chondrogenic tumors.

Free Research Field

整形外科学