Development of a novel treatment strategy for gynecologic cancer targeting the angiogenesis regulator vasohibin-2

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18702
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Koyanagi Takahiro 自治医科大学, 医学部, 講師 (90742122)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 婦人科がん / バソヒビン / 血管新生 / 微小管制御

Outline of Final Research Achievements

Vasohibin 2 (VASH2) is a cancer cell-specific pro-angiogenic factor and also has tubulin detyrosination activity that contributes to microtubule polymerization. We established VASH2 knockout (KO) cell lines for ovarian cancer and cervical cancer cell lines and examined their sensitivity to paclitaxel (PTX). In the VASH2 KO cell lines, PTX exposure inhibited the upregulation of detyrosinated tubulin expression and significantly enhanced the sensitivity to PTX. In the VASH2 KO cells, cyclin B1 expression was increased, and the ratio of cells with cell cycle arrest at middle M phase was increased, leading to enhanced chemosensitivity.
Novel treatment development can be expected from multiple perspectives, such as angiogenesis inhibition and tubulin detyrosination activity.

Free Research Field

婦人科悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

バソヒビン2の有する血管新生促進活性およびチューブリン脱チロシン化酵素活性に着目することで、より多角的な視点から新たな分子標的治療の確立が期待できる。バソヒビン2は成体の正常組織ではほとんど発現しておらず、ノックアウトマウスの表現型にも異常がみられないため、バソヒビン2阻害療法は既存薬にみられるような重篤な副障害を引き起こしにくいと推測される。このように、バソヒビン2阻害療法は、既存薬の感受性増強、副作用の軽減により、がん治療における身体的負担および経済的負担を軽減できる可能性を秘めている。さらには、バソヒビン2を発現する他癌種への治療応用も期待できる。