2022 Fiscal Year Final Research Report
Elucidation of bladder cancer recurrence and progression mechanism focusing on lysophospholipid and establishment of new treatment
Project/Area Number |
19K18567
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56030:Urology-related
|
Research Institution | Fukushima Medical University |
Principal Investigator |
Kataoka Masao 福島県立医科大学, 医学部, 講師 (90554204)
|
Project Period (FY) |
2019-04-01 – 2023-03-31
|
Keywords | 膀胱癌 / 浸潤 / リゾフォスファチジン酸 |
Outline of Final Research Achievements |
Analysis of clinical specimens showed increased expression of lysophosphatidic acid receptor 1 (LPA1) in muscle invasive bladder cancer(MIBC). The human bladder cancer cell line T24 expressing LPA1 was confirmed to have enhanced invasive potential in the presence of physiological urinary concentrations of LPA, with increased Rho activation, ROCK1 phosphorylation, MYPT1 phosphorylation, MLC expression and lamellipodia formation. In addition, increased migration and MMP2 activation by LPA were also observed, and these were identified to be suppressed by LPA1 and ROCK inhibitors. No effect of LPA on proliferative ability was observed. These results suggest that LPA1 and ROCK inhibitors may be novel therapeutic agents to suppress the invasive potential of bladder cancer.
|
Free Research Field |
尿路悪性腫瘍
|
Academic Significance and Societal Importance of the Research Achievements |
膀胱癌の多くは診断時に筋層に浸潤が見られない筋層非浸潤性膀胱癌(NMIBC)である。しかし術後の膀胱腔内再発や再発時に進展する可能性の高い癌でもある。筋層浸潤性膀胱癌(MIBC)となると、膀胱自体の温存は困難で膀胱全摘除術が選択されることが多い。NMIBCでは組織学的因子や腫瘍の数、再発の有無などでリスク分類がなされ、再発予防のための治療が施される。今回の研究結果から、膀胱癌におけるLPA1発現は再発、進展リスクが高い可能性が示唆された。これまで膀胱癌に対する薬物治療は殺細胞性抗癌剤や免疫チェックポイント阻害剤であったが、LPA1阻害剤、ROCK阻害剤が新規治療薬となる可能性が示唆された。
|