The role of HABP2 (Hyaluronan Binding Protein 2) in pancreatic cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Akiyama Yasuki 産業医科大学, 医学部, 助教 (10812191)
• Co-Investigator(Kenkyū-buntansha): 佐藤 典宏 産業医科大学, 医学部, 講師 (20423527)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膵癌 / ヒアルロン酸

Outline of Final Research Achievements

We previously reported hyaluronan (HA) plays critical role in PDAC. However, the mechanisms underlying the accelerated HA processing remain poorly understood. Recently, HABP2 (Hyaluronan Binding Protein 2) has been reported to play a role in promoting migration of cancer cells in response to LMW-HA. The role of HABP2 in PDAC biology is unknown. We therefore analyzed the expression and function of HABP2 in PDAC. To examine the function of HABP2 in PDAC, we established HABP2 knockout clone and HABP2 overexpression clone. We investigated cell migration in association with epithelial-mesenchymal transition (EMT) in these clones. Knockout of HABP2 resulted in decreased cell migration, increased CDH1 mRNA expression, and decreased CDH2 and vimentin mRNA expression. Conversely, forced expression of HABP2 resulted in the opposite to those with knockout clones of HABP2. These findings suggest HABP2 is overexpressed in some PDAC cells and is involved in enhanced migration possibly through EMT.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

ヒアルロン酸（Hyaluronan：HA）は、癌の増殖・運動・浸潤能を高め、転移・播種・血管新生を促進する。膵癌においてHA、特にHA分解酵素で分解された低分子HAが膵癌細胞の遊走・浸潤能を高めることを見出だしたが、そのメカニズムに関しては不明であった。本研究で、膵癌においてHABP2（Hyaluronan Binding Protein 2）が、低分子HAによる癌細胞の遊走能亢進に重要な役割を果たしている可能性を見出した。さらに、HABP2は膵癌の上皮間葉転換に関与している可能性も認めた。今後、HABP2をターゲットとした新たな治療戦略が期待される。