Expression of hyaladherin induced by inactivation of Hippo pathway in malignant mesothelioma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08726
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: Maesawa Chihaya 岩手医科大学, 医歯薬総合研究所, 教授 (10326647)
• Co-Investigator(Kenkyū-buntansha): 谷田 達男 岩手医科大学, 医学部, 教授 (20217144) ; 柴崎 晶彦 岩手医科大学, 医歯薬総合研究所, 助教 (20445109) ; 杉山 徹 岩手医科大学, 医学部, 教授 (40162903)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: RHAMM / Hippo / YAP / 中皮腫

Outline of Final Research Achievements

Malignant mesothelioma is an intractable rare cancer and is a malignant tumor that has a great social impact and is expected to increase in death rate. RHAMM (hyaluronan-mediated motility receptor), a target molecule of the "Hippo-YAP pathway" that plays a central role in the formation of biological properties of malignant mesothelioma, was closely related to invasion and metastasis. Its invasion and metastasis ability depended on hyaluronan-treatment. On the other hand, the effectiveness was not shown in the competitive inhibition experiment using the known candidates such as competitive agent and peptide. The effects of both were downregulation of hyaluronan expression in tumor cells, not the inhibitory effect on binding of both molecules. Research and development of a screening method for inhibitors of RHAMM-hyaluronan interaction inhibition is needed

Free Research Field

実験病理

Academic Significance and Societal Importance of the Research Achievements

難治性の希少癌である胸膜悪性中皮腫の進展機構に、胸水中のヒアルロン酸と腫瘍細胞表面に発現するヒアルアドヘリンRHAMM (hyaluronan-mediated motility receptor)の相互作用が関連していることを明らかにした。この両者の結合阻害は、悪性中皮腫の新たな治療標的となる可能性が示された事は、有効な標準治療の確立されていない中皮腫に新たな治療戦略をもたらす点で社会的意義を認める。