Chondroitin sulfate proteoglycan 4 provides new treatment approach to prevent peritoneal dissemination in ovarian cancer

Abstract

Abstract BACKGROUND: Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect to induce peritoneal disseminations. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell-cell interactions. METHODS: We examined the expression of CSPG4 in clinical samples. The proliferation, migration, and invasion abilities of the CSPG4-knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in vivo model using sh-CSPG4 EOC cell lines. RESULTS: Of clinical samples, 23 (44.2%) samples were expressed CSPG4. CSPG4 was associated with a worse prognosis in EOC patients. When CSPG4 was knockdown, the cell proliferation, migration, and invasion abilities were significantly decreased, and spheroid formation was significantly inhibited compared to control cells. Proteomic analyses showed changes in the expression of proteins related to cell movement pathways. The number of peritoneal disseminations and EOC spheroids in ascites were significantly decreased in sh-CSPG4 mouse models. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor1-inhibited cell. CONCLUSION: CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target to block peritoneal metastasis.