Spatio-temporal analysis of bladder cancer and tumor microenvironment by two-photon excitation imaging in vivo

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18137
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kyoto University
• Principal Investigator: SANO Takeshi 京都大学, 医学研究科, 助教 (60866309)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膀胱癌 / 生体イメージング / 二光子顕微鏡

Outline of Final Research Achievements

Intravital imaging of the mouse bladder with two-photon excitation microscopy found that intravesical instillation of mouse bladder cancer cell line (MB49) induced urothelial collective cell migration (uCCM). The src inhibitor dasatinib (i.v. and p.o.) and the FAK inhibitor PF-573228 (i.v.) almost stopped the uCCM, which fact suggested that the uCCM was dependent on the src/FAK signaling pathway. Surprisingly, the inhibition of uCCM by daily oral administration of dasatinib significantly enhanced orthotopic MB49 bladder tumor development, despite dasatinib inhibiting cell growth in certain types of malignancies. Subcutaneous injection of MB49 resulted in a slight decrease in tumor growth with daily oral adnimistration of dasatinib, suggesting that the uCCM fuctions as a defense mechanism against bladder tumor development.

Free Research Field

膀胱癌

Academic Significance and Societal Importance of the Research Achievements

癌細胞から分泌される物質、あるいは癌細胞に応答して尿路上皮から分泌される物質により尿路上皮が集団運動し、癌細胞から膀胱を守るための防御機構として働くと考えられた。
膀胱癌は経尿道的切除術の後にしばしば膀胱内に播種再発する。MB49による同所性膀胱癌マウスモデルは、膀胱内播種再発を模したモデルとされており、本研究の結果は、集団運動を誘導する物質を同定し、防御機構を強化することができれば、経尿道的切除術後の播種再発を予防できる可能性を示唆すると考えられる。