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ID 110112
Title Alternative
膀胱癌進展、浸潤におけるHGF-MET-MMP1 signalingの関与とMET阻害薬、カボザンチニブの有効性
Author
Daizumoto, Kei Tokushima University
Dondoo, Tsogt-Ochir Tokushima University
Yamamoto, Hiroki Tokushima University
Nakatsuji, Hiroyoshi Tokushima University
Keywords
HGF
MET
Cabozantinib
MMP
Bladder cancer
HGF-MET
Matrix Metalloproteinase 1
Content Type
Thesis or Dissertation
Description
OBJECTIVES To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies.We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells.
METHODS We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib.
RESULTS MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells.
CONCLUSIONS These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscleinvasive BCa.
Journal Title
Urology
ISSN
00904295
NCID
AA0087924X
Publisher
Elsevier
Volume
101
Start Page
169.e7
End Page
169.e13
Published Date
2016-12-21
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704271007.pdf
論文本文:k3020_fulltext.pdf
著者の申請により要約(2017-05-19公開)に替えて論文全文を公開(2018-12-12)
本論文は, 著者Terumichi Shintaniの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3020号
Diploma Number
甲医第1324号
Granted Date
2017-03-06
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences