Peritoneal metastatic gastric carcinoma cells exhibit more malignant behavior when co-cultured with HMrSV5 cells

Abstract

Metastasis and recurrence are major causes of death in gastric cancer patients. Because there are no obvious clinical symptoms during the early stages of metastasis, we sought to isolate highly invasive metastatic gastric cancer cells for future drug screening. We first established a mouse model to observe gastric cancer metastasis in vivo. The incidence of peritoneal metastasis of gastric cancer was much higher than liver or lymph metastasis. Peritoneal metastatic and non-metastatic NUGC-4 cells were isolated from the mouse model. Cell proliferation was measured using CCK-8 assays, while migration and invasion were investigated in Transwell assays. Proteins involved in epithelial-mesenchymal transition were detected by Western blotting. Metastatic gastric carcinoma cells were more proliferative and invasive than primary NUGC-4 cells. The supernatants of metastatic gastric carcinoma cells notably altered the morphology of HMrSV5 peritoneal mesothelial cells and promoted their epithelial-mesenchymal transition. Moreover, primary or metastatic gastric cancer cells co-cultured with HMrSV5 cells markedly increased cancer cell proliferation and invasiveness. Moreover, peritoneal metastatic gastric carcinoma cells in the presence of HMrSV5 cells exhibited most malignant behaviors. Thus, peritoneal metastatic gastric carcinoma cells exhibited high capacities for proliferation and invasion, and could be used as a new drug screening tool for the treatment of advanced gastric cancer and peritoneal metastatic gastric cancer.

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

“…However, a thickened PMC layer has been observed near the peritoneal metastasis lesions of both colorectal and pancreatic cancers [ 68 , 69 ]. In addition, the proliferative and invasive ability of PMCs was found to be significantly enhanced when co-cultured with the NUGC4 gastric cancer cell line [ 70 ]. None of these studies supported the perspective that senescent PMCs promote tumor progression.…”

“…PMCs can transition to the MMT phenotype under co-culture with cancer cells. For example, co-culturing of the highly metastatic MKN45 cell line and the PMC line HMrSV5 induced the MMT phenotype in PMCs, and the mesenchymal PMCs could in turn enhance the invasiveness and metastasis of the gastric cancer cells [ 70 ]. Furthermore, PMCs can be affected by soluble factors from the cancer environment.…”

BGN/FAP/STAT3 positive feedback loop mediated mutual interaction between tumor cells and mesothelial cells contributes to peritoneal metastasis of gastric cancer

“…CAF markers, which mainly consist of fibroblast activation protein (FAP), α-smooth muscle actin (α-SMA), and Vimentin, promote tumor progression [9][10][11]. Studies also show that tumor cells exhibit more malignant behavior when co-cultured with CAFs [12][13][14].…”