Personalized treatment strategy for pancreatic cancer targeting hyaluronan metabolism

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Sato Norihiro 産業医科大学, 医学部, 講師 (20423527)
• Co-Investigator(Kenkyū-buntansha): 平田 敬治 産業医科大学, 医学部, 教授 (70269059)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵癌 / ヒアルロン酸

Outline of Final Research Achievements

We investigated transcriptional profiling of genes involved in HA synthesis (including HAS2 and HAS3) and degradation (including HYAL1 and KIAA1199) in a panel of PDAC cell lines and primary tissues.　 A subset of PDAC (20% of cell lines and 25% of tissues) showed overexpression of multiple genes encoding both HA-synthesizing and HA-degrading enzymes, displaying a phenotype defined as an HA activated-metabolism phenotype (HAMP). Interestingly, HAMP+ cells were more susceptible to the treatment with an HA synthesis inhibitor and HA degradation inhibitor than HAMP- cells. Patients with HAMP+ tumors were significantly associated with shorter survival than those with HAMP- tumors (P = 0.049).　 he present study identified a novel phenotype, HAMP, characterized by activation of HA metabolism pathways, in PDAC. HAMP should be further investigated as a prognostic marker as well as a target for personalized medicine.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

膵癌の生存率は依然として改善しておらず、画期的な治療法の開発が急務である。今回、膵癌の間質に着目し、細胞外マトリックスの成分であるヒアルロン酸の代謝についての研究を行った。膵癌ではヒアルロン酸の代謝が亢進しており、低分子に分解したヒアルロン酸を利用しながら悪性度を高めている可能性が示唆された。したがって、このヒアルロン酸代謝経路をターゲットとした治療戦略は、膵癌の新たな治療法となることが期待される。国内外で同じような研究成果の報告はなく、学術的および臨床的にも重要な発見であると考えられる。