Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis.
Peritoneal metastasis is a primary cause of mortality in patients with gastric cancer. Urokinase-type plasminogen activator (uPA) has been demonstrated to be associated with tumor cell metastasis through the degradation of the extracellular matrix. The present study aimed to investigate the mechanisms of the uPA system in gastric cancer with peritoneal metastasis. Expression of uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in four gastric cell lines (AGS, SGC7901, MKN45 and MKN28) was measured by semiquantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting. uPA activity was detected using a uPA activity kit. Peritoneal implantation models of rats were established by injecting four gastric cancer cell lines for the selection of the cancer cells with a high planting potential. Biological behaviors, including adhesion, migration and invasion, were determined using a methyl thiazolyl tetrazolium assay. Expression of the uPA system was observed to be highest in the SGC7901 cells among the four gastric cell lines. uPA activity was observed to be highest in the MKN45 cells and lowest in the AGS cells. Furthermore, peritoneal implantation analysis demonstrated that no peritoneal tumors were identified in the AGS cells, whilst the tumor masses observed in the SGC7901 and MKN45 cells were of different sizes. The survival times of the rats injected with the MKN28 and SGC7901 cells were longer than those of the rats injected with the MKN45 cells. Antibodies for uPA, uPAR and PAI-1 in the uPA system had the ability to inhibit the adhesion, migration and invasion of peritoneal metastasis in the gastric cancer cells. The results of the present study demonstrated that the uPA system was positively associated with peritoneal metastasis in gastric cancer.
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Youcheng
Y
Ding
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Hui
H
Zhang
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Aiguo
A
Lu
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Zhuqing
Z
Zhou
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Mingan
M
Zhong
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Dongwei
D
Shen
Department of General Surgery, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, P.R. China.
Xujing
X
Wang
Department of Gastroenterological Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Zhenggang
Z
Zhu
gastric cancer; peritoneal metastasis; urokinase-type plasminogen activator