高转移和低转移人肺癌细胞中纤溶酶原激活物系统各组分表达的分析

Analysis of expressions of components in the plasminogen activator system in high- and low-metastatic human lung cancer cells.

作者信息

He C, He P, Liu L P, Zhu Y S

机构信息

Department of Molecular Genetics, Shanghai Medical University, Shanghai, 200032, China.

出版信息

J Cancer Res Clin Oncol. 2001;127(3):180-6. doi: 10.1007/s004320000192.

DOI:10.1007/s004320000192

PMID:11260863

Abstract

PURPOSE

To determine the expressive patterns of the components of the plasminogen activator system in human large-cell lung carcinoma strains and to analyze the effects of the patterns on tumor invasion and metastasis.

METHODS

The in vitro and in vivo invasive and metastatic potential of two human large-cell lung carcinoma strains with high (strain 95D) and low (strain 95C) metastatic potential was further confirmed by the Boyden chamber model and nude mice model. After this, the expressions of the components of the plasminogen activator system--including urokinase-type and tissue-type plasminogen activator (uPA and tPA), urokinase receptor (uPAR), and type-1 and type-2 plasminogen activator inhibitor (PAI-1 and PAI-2) in strain 95D and 95C cells--were determined by RT-PCR and immunohistochemical staining. The effects of monoclonal antibodies of uPA, uPAR, and PAI-1 on the invasive potential of strain 95D cell line were also evaluated.

RESULTS

Strain 95D cells were found to have a stronger in vitro and in vivo invasive and metastatic potential than strain 95C cells. In the former, the average number of infiltrating cells in the in vitro model in one field of vision (40055) was 73.75 +/- 7.42, while in the latter, it was 56.33 +/- 6.28 (P < 0.001). Lung metastatic loci were observed in all six nude mice inoculated with 95D cells (6/6), but not in any of the nude mice inoculated with 95C cells (0/6). The high-metastatic strain 95D cells expressed higher uPA and uPAR and lower tPA and PAI-2 than the low-metastatic strain 95C cells. The PAI-1 expressions in both 95D and 95C cells were almost the same. Monoclonal antibodies of uPA and uPAR greatly reduced the invasive potential of strain 95D cells in vitro.

CONCLUSIONS

These data suggest that the invasive and metastatic potential of human large-cell lung carcinoma cell lines is associated with differential expressions of the components of the plasminogen activator system and that the determination of these components may be used as a marker for judging clinically the possibility of tumor metastasis as well as the prognoses of patients.

摘要

目的

确定纤溶酶原激活物系统各组分在人大细胞肺癌细胞株中的表达模式，并分析这些模式对肿瘤侵袭和转移的影响。

方法

采用Boyden小室模型和裸鼠模型进一步证实两株具有高转移潜能（95D株）和低转移潜能（95C株）的人大细胞肺癌细胞株的体外和体内侵袭及转移能力。在此之后，通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学染色法检测95D株和95C株细胞中纤溶酶原激活物系统各组分的表达，这些组分包括尿激酶型和组织型纤溶酶原激活物（uPA和tPA）、尿激酶受体（uPAR）以及1型和2型纤溶酶原激活物抑制剂（PAI-1和PAI-2）。还评估了uPA、uPAR和PAI-1单克隆抗体对95D细胞株侵袭能力的影响。

结果

发现95D株细胞比95C株细胞具有更强的体外和体内侵袭及转移能力。在前者中，体外模型中一个视野（400×55）内浸润细胞的平均数为73.75±7.42，而在后者中为56.33±6.28（P<0.001）。接种95D细胞的6只裸鼠全部观察到肺转移灶（6/6），而接种95C细胞的裸鼠均未观察到肺转移灶（0/6）。高转移株95D细胞比低转移株95C细胞表达更高的uPA和uPAR，以及更低的tPA和PAI-2。95D和95C细胞中的PAI-1表达几乎相同。uPA和uPAR单克隆抗体在体外大大降低了95D细胞株的侵袭能力。