|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1994 : ¥1,200,000 (Direct Cost : ¥1,200,000)
We have established a new in vivo model for studying invasion and metastasis of bladder cancer.The animal model system consisted of a rat bladder transplanted in the retroperitoneum of a nude mouse and connected with a subcutaneous reservoir.The cells we used were rat bladder carcinoma cell lines (LMC19, MYU3L), murine bladder carcinoma cell line (MBT-2), and human transitional cell carcinoma cell lines (SK-S,SK-I). The human cell lines (SK-S,SK-I) were newly establishied from patients with bladder tumor and renal pelvic tumor.In vivo study, SK-S cells formed superficial tumors.MBT-2, MYU3L,and SK-I tumors were invasive, but non-metastatic ones.LMC19 tumors were invasive and metastatic ones.
Overexpression of MMP-2 into MYU3L cells transformed the parental cells (invasive/non-metastatic) to the metastatic phenotype.On the other hand, the metastatic potential was highly suppressed by the introduction of TIMP1, or TIMP2 to LMC19 cells.The expression of carbohydrate antigen was altered between SK-S cells (superficial type) and SK-I cells (invasive type). Reactivity to BSA,ECA,and PNA lectin were increased on the cell surface of SK-I cells.
Our results support the evidence that the invasive or metastatic potential can be closely related with MMP expression and altered expression of carbohydrate antigen.
以上より,膀胱癌においても,浸潤転移能の獲得には,type IV collagenase,特にMMP-2の関与が重要であることが示された。また,癌細胞膜表面の複合糖質糖鎮の構造変化も,腫瘍の悪性化に関与していることが示唆された。