Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

Abstract

Abstract. 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.

Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts

“…GC cells co‐cultured with adipocytes exhibited increased invasion ability (Figure 4). Previous studies have shown that IL‐6 and PAI‐1 are key factors that enhance the invasiveness of GC cells 33,34 . Our results were consistent with these reports; the expression levels of IL‐6 and PAI‐1 were significantly increased in the adipocytes co‐cultured with GC cells (Figure 3D).…”

“…Previous studies have shown that IL-6 and PAI-1 are key factors that enhance the invasiveness of GC cells. 33,34 Our results were consistent with these reports; the expression levels of IL-6 and PAI-1 were significantly increased in the adipocytes co-cultured with GC cells (Figure 3D). There is a possible underlying mechanism that increases the expression levels of IL-6 and PAI-1.…”

Experimental and Clinical Evidence Supports the Use of Urokinase Plasminogen Activation System Components as Clinically Relevant Biomarkers in Gastroesophageal Adenocarcinoma

“…uPAS expression (uPA, uPAR, PAI-1), however, did not alter between malignant and non-malignant peritoneum within the patients with peritoneal metastases [88]. Translational investigations confirm the role of altered uPAS expressing cell lines in the development of peritoneal metastasis [89] and increased ascites formation [90].…”

Quercetin Has Antimetastatic Effects on Gastric Cancer Cells via the Interruption of uPA/uPAR Function by Modulating NF-κb, PKC-δ, ERK1/2, and AMPKα

“… 19 Based on the analysis to 105 GC specimens, Zhang et al 20 found that uPA and uPAR mRNA expression rates in infiltrating-type cases, stage III-IV, vessel invasion, lymphatic metastasis, and distant metastasis were significantly higher than those in expanding-type cases, stage I-II, non–vessel invasion, non–lymphatic metastasis, and non–distant metastasis, respectively, thereby suggesting that uPA and uPAR expressions can serve as prognostic markers of GC. Semiquantitative RT-PCR and ELISA measurements conducted by Ding et al 21 showed higher expressions of uPA and uPAR in peritoneal metastatic lesions than in normal peritoneal tissues. High levels of uPA and uPAR may predict an adverse outcome in patients with GC.…”