2000 Fiscal Year Final Research Report Summary
Basic study for the prevention of recurrence by inhibition of cell adhesion and migration in superficial bladder cancer.
| Project/Area Number |
11671533
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Hokkaido University |
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Principal Investigator |
HARABAYASHI Toru Hokkaido Univ., Medical, Hospital, Inst., 医学部・附属病院, 助手 (70301900)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOHARA Nobuo Hokaido Univ., Medical, Hospital, Lect., 医学部・附属病院, 講師 (90250422)
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| Project Period (FY) |
1999 – 2000
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| Keywords | bladder cancer / recurrence / intravesical dissemination / cell-extracellular matrix adhesion / integrin / orthotopic transplantation model / intracellular signaling pathway |
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| Research Abstract |
Superficial bladder cancer is characterized by its multiplicity and recurrence, which is supposed to be caused by intraluminal dissemination. In this step, adhesion and migration of cancer cells on extra cellular matrices mediating through membranous protein and intracellular signaling pathways are of great importance.
1) To examine in vivo intraluminal dissemination, we developed a murine orthotopic implantation model of bladder cancer. After the pretreatment by EDTA, cancer cell suspensions were injected to the murine bladder through the urethral catheter and kept in the bladder by 3-hour urethral ligation. The ability of intraluminal dissemination was examined in the bladder cancer cell lines using this method. The 6 cell lines were classified into 3 groups ; highly growing cell lines (UMUC-2 : 100%, KU7 : 100% and UMUC-6-dox : 100%), and a low growing cell line (EJ : 18%), and no growing cell lines (KU-1 : 0%, DAB-1 : 0%). 2) Expressions of cell adhesion molecules, adhesion mediating signaling molecules were examined by Western blot analysis. Highly growing cell lines showed that reduction of integrin beta-4, cadherin and beta-catenin, although the expressions of FAK, paxillin, alpha-catenin, Csk and Crk varied between 3 groups. From these results, the expression of integrin beta-4 and cadherin played an important role in intraluminal dissemination. 3) The expression and distribution of integrin beta-4 was examined using surgically resected specimen from bladder cancer patients. The expression and distribution of integrin beta-4 was strongly correlated with T-stage and metastasis. These results suggested that control of cell adhesion protein and mediating signals could inhibit the recurrence of the bladder cancer.
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[Publications] Takafumi Watanabe, Nobuo Shinohara, Ataru Sazawa, Toru Harabayashi, Yoshifumi Ogiso, Tomohiko Koyanagi, Mitsuyoshi Takiguchi, Akira Hashimoto, Noboru Kuzumaki, Motoyuki Yamashita, Motoyoshi Tanaka, H.Barton Grossman, William F.Benedict: "An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies."Cancer Gene Therapy. 7. 1575-1580 (2000)
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「研究成果報告書概要(欧文)」より
