Analysis of possible role of u-PAR and PAI in cancer metastasis

探讨u-PA、u-PAR和PAI在肿瘤侵袭转移中的作用。胃肠道癌组织中PAI-1和PAI-2的表达明显高于癌旁正常组织。(2)高水平的u-PA组结直肠癌预后较差。(3)PAI-2水平低的肿瘤有向远处转移的倾向，提示PAI-2可能具有抑制淋巴结转移的作用。(4)我们成功地从手术标本中建立了含有不同水平u-PA的结肠癌异种移植瘤。用人肿瘤细胞株研究PAI-1和PAI-2，发现u-PA以剂量依赖方式促进细胞增殖，PAI-2以剂量和时间依赖方式抑制细胞增殖。利用人结肠癌自发转移模型研究了PAI-1和PAI-2对肿瘤生长和转移的影响，结果表明，PAI-2治疗组原发肿瘤体积明显小于对照组和PAI-1治疗组，肝转移率低于对照组，提示PAI-2可能具有抑制肿瘤生长和转移的作用。

The role of u-PA,u-PAR and PAI for invasion and metastasis of cancer was investigated.a) clinical study(1) The levels of u-PA,PAI-1 and PAI-2 in cancer tissues of gastrointestinal tract showed significantly higher than those of adjacent normal mucosa.(2) High u-PA group showed poor prognosis in colorectal cancer.(3) Tumors with lower PAI-2 levels tended to metastasize to remote lymph nodes suggesting that PAI-2 might have a role to suppress lymph node metastasis.(4) We succeeded to establish human colon cancer xenografts which contained different levels of u-PA from surgical specimens.b) in vitro studyAlterations of cell proliferation and invasion by u-PA,PAI-1 and PAI-2 were investigated using human tumor cell lines.The results showed that u-PA accelerated cell proliferation in a dose dependent manner, and PAI-2 suppressed in dose and time dependent manner. Moreover, u-PA accelerated cell invasion, though PAI-1 and PAI-2 suppressed it significantly.c) in vivo studyThe effects of PAI-1 and PAI-2 on tumor growth and metastasis were investigated using spontaneous metastatic models of human colon carcinoma.The results showed that the size of primary tumor was significantly lower in PAI-2 treated group than those in control and PAI-1 treated groups, and the rate of liver metastasis was lower in PAI-1 and PAI-2 treated groups than that in control group.We conclude that PAI-2 may suppress tumor growth and metastasis.