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

（1）胃肠道癌组织中u-PA、派-1和PAI-2的水平均显著高于癌旁正常胃粘膜组织;（2）胃肠道癌组织中u-PA、派-1和派-2的水平均显著高于正常胃粘膜组织。(2)高u-PA组结直肠癌预后差。(3)派-2水平较低的肿瘤倾向于向远处淋巴结转移，提示派-2可能具有抑制淋巴结转移的作用。(4)B）体外研究u-PA、派-1和派-2对人结肠癌细胞增殖和侵袭的影响，结果表明：u-PA以剂量依赖方式促进细胞增殖，派-2以剂量和时间依赖方式抑制细胞增殖。此外，u-PA促进细胞侵袭，而派-1和派-2显著抑制细胞侵袭。c）体内研究采用人结肠癌自发转移模型研究派-1和派-2对肿瘤生长和转移的影响。结果显示，派-2治疗组的原发肿瘤大小显著小于对照组和派-1治疗组，派-1和派-2治疗组肝转移率低于对照组，提示派-2可能抑制肿瘤的生长和转移。

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.