Study Of The Matriptase Expression Regulation And Its Relationship With Invasion And Metastasis Of Gastric Cancer

BackgroundGastric cancer (GC) still remains high morbidity and mortality in the worldwide. It hasbeen threatening the life of human, and locating in the world’s fourth most commonmalignancy. Although the treatment method of gastric cancer has been developed in recentyears and the comprehensive treatment models are continuously improved, including surgery,radiotherapy, chemotherapy and immuno-biological therapy, due to the lack of certainspecific signs and symptoms in the early stage, patients with gastric cancer were often foundin the advanced stage, with less than25%of five-year survival rate. The pathogenesis andtreatment of gastric cancer showed high incidence, mortality and transfer rate, but lowdiagnosis rate in early stage, resection rate and5-year survival rate in the clinical practice.Currently, surgery is the most common treatment of gastric cancer. Postoperative recurrenceand metastasis are the biggest difficulties in treatment of gastric cancer, bringing great painsto patients. Therefore, it is very important to study the mechanism of invasion and metastasisof gastric cancer.The type II transmembrane serine proteases (TTSPs) were the proteolytic enzymeslocated on the cell membranes through the N-terminal transmembrane region. They candegrade the extracellular matrix (ECM) and cell membranes and inhibit the invasion andmetastasis of tumors. Matriptase, one member of TTSPs family, was found playing animportant role in the metastasis and invasion of colorectal cancer. However, it had not beenreported to impact on the abilities of invasion and metastasis of gastric cancer cells.ObjectiveThe expression levels of Matriptase were detected in clinical cases of gastric cancer andgastric cancer cell lines to analyze the correlation of Matriptase expression toclinicpathological factors, invasion and metastasis of gastric cancer. The possible mechanism of Matriptase in the occurrence, development, invasion and metastasis of gastric cancer wasalso analyzed.Results1. Compared to the adjacent non-cancerous gastric mucosa, the positive expression levelof Matriptase in gastric cancer tissues was significantly decreased; the protein expressionlevel of Matriptase in gastric cancer tissues was related to the size of gastric cancer lesion,depth of infiltration, TNM stage of tumor and number of lymph node metastasis (P <0.05).2. Matriptase siRNA was successfully constructed and efficiently transferred intoMGC803cells. An overexpression vector Matriptase was successfully constructed andefficiently transferred into MKN45cells. The silent efficiency of Matriptase mRNA inMatriptase siRNA group was not significantly different from that in the negative controlgroup or blank control group; and the abilities of migration and invasion were increased inMatriptase siRNA group. The mRNA expression of Matriptase in Matriptase overexpressiongroup was obviously higher than those in the negative control group and blank control group(P<0.01); and the abilities of migration and invasion were decreased in Matriptaseoverexpression group (P<0.01).Conclusion1. The low level of Matriptase expression in gastric cancer was not only related to thedevelopment and metastasis of gastric cancer, but also used as one of the indicators to judgethe prognosis of patients with gastric cancer.2. The mRNA expression of Matriptase in gastric cancer MGC803cells could beeffectively inhibited by Matriptase interference. And the migration and invasion of MGC803cells could be enhanced by the silent expression of Matriptase in gastric cancer MGC803cells.3. The overexpression of Matriptase could increase the mRNA expression of Matriptasein gastric cancer MKN45cells and reduce the abilities of migration and invasion of MKN45cells.