CD9-positive exosomes from cancerassociated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells

Abstract

Background: Crosstalk between cancer cells and fibroblasts is crucial for tumour progression. It has been reported that exosomes derived from cancer cells play an important role in the intracellular communications involved in the development of carcinoma. However, the role of exosomes from fibroblasts remains unclear. This study aimed to clarify the effect of exosomes from fibroblasts on the motility of gastric cancer cells. Methods: 5 gastric cancer cell lines were used: OCUM-12, NUGC-3, MKN45, FU97 and MKN74. 2 cancer-associated fibroblasts (CAFs) were used. CD9 expression of exosomes from fibroblasts was examined by western blot. The effect of exosomes on the motility of cancer cells was analysed by migration assays. MMP2 was examined by RT-PCR or gelatin zymography. Then, CD9 and MMP2 expressions of 619 gastric cancers were analysed by immunohistochemistry. Results: Exosomes from CAFs were taken into scirrhous-type gastric cancer cells, namely OCUM-12 cells and NUGC-3 cells, but not into other types of gastric cancer cells. Exosomes from CAFs were positive for CD9. Exosomes from CAFs significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells, which was inhibited by anti-CD9 antibody or CD9-siRNA. MMP2 expression of OCUM-12 and NUGC-3 cells was significantly decreased by CD9-siRNA. 116 CD9-positive cases were significantly correlated with scirrhous-type gastric cancer, lymph node metastasis and venous invasion. The 5-year survival rate of patients with CD9-positive tumours was significantly lower (Po0.001) than in those with CD9-negative tumours. Conclusions: CD9-positive exosomes from CAFs might stimulate the migration ability of scirrhous-type gastric cancer cells.