The Destruction Of Gastric Cancer Cells To Peritoneal Mesothelial Cells

PartⅠInteractions of gastric cancer cells and human peritoneal mesothelial cells involved in peritoneal fibrosis and peritoneal carcinomatosis.This study examined the mechanism by which the gastric cancer cells lead to early peritoneal metastasis. Injuryed mesothelial cells were co-incubated with marked gastric cancer cells for 30 min, and then examined under fluorescence microscope for adhersion.18 male C57BL/6 rats were randomly allocated into three groups:control group, normal rats; DMEM group:rats were treated with intraperitoneal injection of DMEM on days 1,3,5,7 for 4 weeks; supernatants group:rats were treated with intraperitoneal injection of supernatants from gastric cancer cells on days 1,3,5,7 for 4 weeks; The parietal thickness was measured with HE and masson stains. Human peritoneal mesothelial cell (HPMC) line HMrSV5 was co-incubated with gastric cancer cell supernatant. Morphological changes in HPMC were observed under scan electron microscope phase-contrast microscope. To confirm whether injuryed HPMC could affect gastric cancer cells. We examed the abilitys of invasion and metastasis in gastric cancer cells by Millicell. Results:Mesothelial cells can prevent cancer cell infiltration into sub-mesothelial connective tissue. The supernatants could induce peritoneal fibrosis. HE and masson stains show the parietal thickness of the rats in supernatants group was significantly increased compared with control group. The results showed that conspicuous morphological changes were observed in HPMC after treatment with the supernatants of gastric cancer cells. The supernatants could induce cytoskeleton reconstruction of HPMC. The injuryed mesothelial cells could up-regulate the abilitys of invasion and metastasis in gastric cancer cells. Conclusion: These findings demonstrated that gastric cancer cells can induce the peritoneal fibrosis through supernatants in the early peritoneal metastasis. Wild mesothelial cells can prevent cancer cell infiltration into sub-mesothelial connective tissue.However, in contrary, injuryed mesothelial cells could up-regulate the abilitys of invasion and metastasis in gastric cancer cells. PartⅡDestruction of Gastric Cancer Cells to Mesothelial Cells by Apoptosis in the Early Peritoneal MetastasisThis study examined the mechanism by which the gastric cancer cells lead to early peritoneal metastasis. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with the supernatants of gastric cancer cells. Morphological changes of HMrSV5 cells were observed. The cell damage was quantitatively determined by MTT assay. The apoptosis of HMrSV5 cells was observed under transmission electron microscope. Acridine orange/ethidium bromide-stained condensed nuclei was detected by fluorescent microscopy and flow cytometry. The expressions of Bcl-2 and Bax was immunochemically evaluated. The results showed that conspicuous morphological changes of apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. The supernatants could induce apoptosis of HMrSV5 cells in a time-dependent manner. The supernatants could up-regulate the expression of Bax and suppress that of Bcl-2 in HMrSV5 cells. These findings demonstrated that gastric cancer cells can induce the apoptosis of HPMCs through supernatants in the early peritoneal metastasis. The abnormal expressions of Bcl-2 and Bax may contribute to the apoptosis. Anti-apoptosis drugs promise to be adjuvant chemotherapeutic agents in the treatment of peritoneal metastasis of gastric cancer. PartⅢTransforming Growth Factor Betal produced by autocrine/paracrine in peritoneal affect the function and morphology of mesothelial cells and promote peritoneal carcinomatosisHuman peritoneal mesothelial cells (HMPCs) have been proved to protect against peritoneal metastasis of tumor in intact mesothelia.We have previously reported that peritoneal apotosis induced by gastric cancer cells prior to peritoneal implantation may provide a favorable environment for peritoneal metastases. In this study we investigated the effects of TGF-β1 on tumour-mesothelial interaction. The level of various soluble factors were mesured. The expressions of smad 2,3 and phosphorylated smad 2,3 were immunochemically evaluated. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with gastric cancer cells, TGF-P, gastric cancer cells+ TGF-β1 inhibitor SB431542, respectively. Morphological changes of HMPC cells were observed. The cell damage was quantitatively determined by fluorescent microscopy and flow cytometry. Tumour-mesothelial cell adhesion was examined. The results showed that a significantly elevation of TGF-β1 expression in each gastric cancer cell line. Phosphorylated-smad2,3 expressions increased after gastric cancer cells treatment. Mesothelial cells exposed to gastric cancer cells or TGF-β1 became exfoliation and appeared injury, while blocking TGF-β1 partly inhibited these effects. We suggest that soluble factors, such as TGF-P 1, produced by autocrine/paracrine in peritoneal cavity affect the function and morphology of mesothelial cells so that the resulting environment becomes favorable for peritoneal metastases.