| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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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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