| Objective: According to the latest annual statistics,gastric cancer is the third leading cause of cancer-induced deaths,among all malignant tumors.Because of lacking of obvious clinical symptoms,most gastric cancer patients who were first time diagnosed were in advanced stages.Peritoneal metastasis is common in advanced gastric cancer,meanwhile,peritoneal metastasisis is the main reason for the failure of gastric cancer surgery,which leads to a poor prognosis in advanced gastric cancer patient.In recent years,due to the gradual deepening of the concept of peritoneal microenvironment,we have learned more about the processes and mechanisms related to peritoneal metastasis of gastric cancer.The structure of the peritoneum tissue is simple which is just a compact area composed of monolayer mesothelial cells(MCs),fibroblasts,mast cells,macrophages and vascular connective tissue.Because of its structural and biological characteristics,integrated peritoneal mesothelial cells layer is the first barrier that prevents tumor peritoneal metastasis.However,due to tumorigenesis,the peritoneal microenvironment has changed.According to the "seed and soil" theory,the peritoneal mesothelial cells changed with the peritoneal microenvironment alteration conducted a barrier of peritoneum which was a more suitable soil for tumorigenesis.Senescence of human peritoneal mesothelial cells is one of the alteration in peritoneal microenvironment.Aging itself is a normal biological phenomena,however,abnormal occurrence of aging can often lead to tumors.This study first simulated the peritoneal environment and directly induced peritoneal mesothelial cells through the gastric cancer supernatant to explain the aging mechanism from the various manifestations of aging.Finally,the effects of senile peritoneal mesothelial cells and young peritoneal mesothelial cells on the adhesion,migration and invasion of gastric cancer cells were compared,and the importance of peritoneal mesothelial cell senescence in peritoneal metastasis of gastric cancer was further clarified.Methods:1.Peritoneal mesothelial cells were extracted from human normal peritoneal tissue,and mesothelial cells were induced with conditioned medium derived from gastriccancer cells.Relevant indicators were measured around the various processes of aging,such as the expression of aging-related β-galactosidase and CX43 protein.Moreover,the expression of γ-H2 A.X was measured by immunofluorescence and the expression of P16 was measured by RT-PCR.2.To explore the specific process of peritoneal mesothelial cells promoting peritoneal metastasis of gastric cancer after aging.In vitro experiments use young peritoneal mesothelial cells and senescent peritoneal mesothelial cells to induce gastric cancer cells,respectively,so as to determine the specific process of senescent peritoneal mesothelial cells promoting peritoneal metastasis of gastric cancer cells by comparing the differences in their adhesion,migration and invasion capabilities.Results: 1.After the gastric cancer supernatant induced peritoneal mesothelial cells,the expression of senescence-related β-galactase increased,the expression of CX43 decreased,the expression of DNA damage-related protein γ-H2 A.X increased,and the expression of aging-related gene P16 increased.2.Compared with young peritoneal mesothelial cells,senescent peritoneal mesothelial cells significantly promoted the ability of gastric cancer cells to adhere,migrate,and invade.Conclusion: Gastric cancer cells can stimulate the aging of peritoneal mesothelial cells by secreting a series of biologically active substances.The aging manifestations include increased senescence-associated β-galactosidase production,reduced gap junction protein,increased aging-related DNA activation damage response,and aging-related increased gene expression.At the same time,senescent human peritoneal mesothelial cells can promote adhesion,migration and invasion of gastric cancer cells. |
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