Analysis of PFKFB3 expression in tumor cells and tumor endothelial cells in hepatocellular carcinoma and new therapy exploration

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18083
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Matsumoto Kenichi 大阪大学, 医学系研究科, 招へい教員 (60781721)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 腫瘍血管正常化 / 解糖系 / 肝細胞癌

Outline of Final Research Achievements

We aimed to investigate the significance of PFKFB3 in HCC, and the effects of the PFKFB3 inhibitor, PFK15, in HCC tumor cells and tumor endothelial cells. Double immunofluorescent staining of PFKFB3 and CD31 in HCC tissues revealed that high PFKFB3 expression in both tumor cells and tumor endothelial cells was significantly correlated with poor prognosis. PFK15 s pressed proliferation of HCC cell line and tumor endothelial cells in vitro. In a subcutaneous tumor model of the HCC cell line with tumor endothelial cells, PFK15 suppressed tumor growth and induced apoptosis. Moreover, PFK15 treatment induced tumor vessel normalization, decreasing vessel diameter with pericyte attachment and improving vessel perfusion. High PFKFB3 expression in both tumor cells and tumor endothelial cells was i tified as a novel prognostic marker in HCC. Targeting PFKFB3 via PFK15 might be a promising strategy for suppressing tumor growth and inducing tumor vessel normalization.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌に対する最も有効な治療法は外科手術であるが、根治切除後にも高率に肝内転移あるいは肝外転移を来す（5年無病生存率は約30%）。一方、他癌腫と比較しても肝細胞癌に対する全身化学療法の選択肢は非常に限られており、新規治療薬の開発は喫緊の課題である。当研究により、肝細胞癌に対して、PFKFB3阻害薬PFK15が糖代謝制御により腫瘍細胞増殖を抑制し、また腫瘍血管正常化を誘導できることが明らかとなった。この結果はPFKFB3を標的とした治療が肝細胞癌の転移を抑制し、再発の減少につなげられる可能性を示唆する。