Research for a sensitizer of molecular targeted therapy by a regulation of extra-cellular matrix in bone and soft tissue sarcomas

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: URAKAWA Hiroshi 名古屋大学, 医学(系)研究科(研究院), 特任助教 (60584753)
• Research Collaborator: NISHIDA Yoshihiro 名古屋大学, 医学系研究科, 准教授 (50332698) ; KOZAWA Eiji 名古屋大学, 医学部附属病院, 病院助教 (60635572) ; IKUTA Kunihiro 名古屋大学, 医学部附属病院, 医員 (40732657) ; HAMADA Shunsuke 名古屋大学, 医学部附属病院, 医員 (90747289)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 骨軟部肉腫 / 細胞外マトリックス / ヒアルロン酸

Outline of Final Research Achievements

Hyaluronan (HA) is known to have pivotal roles in the growth, migration and invasion of malignant tumors. We initially investigated the prognostic value of HA in patients with malignant peripheral nerve sheath tumors (MPNST). In multivariate analysis, large tumor size was an independent prognostic factor for overall survival, and HA expression and tumor size were independent prognostic factors for disease-free survival. We also investigated the effects of 4-Methylumbelliferone (MU) on bone and soft tissue sarcoma cell lines. MU treatment inhibited extra-cellular matrix, HA accumulation, cell growth, cell motility, and cell invasiveness. In vivo, administration of MU inhibited the tumor growth in isograft models of Rat chondrosarcoma cells. These data suggest that MU might be a therapeutic candidate for sarcomas via suppression of HA synthesis and accumulation. HA-targeting therapy may have potential as a sensitizer of molecular targeted therapy.

Free Research Field

整形外科学