A proportion of
gastric cancer (GC) patients suffer from peritoneal
metastasis (PM) in the late stage of
tumor and these patients have a poor prognosis. To provide more care for GC patient with PM, a deeper exploration of the molecular characteristics of GC-PM is needed. Here we performed the in vitro and in vivo study to illustrate the effect of HOXA11 over-expressed GC cells on peritoneal mesothelial cells (HMrSV5), transcriptomics analyses of HMrSV5 cells co-cultured with HOXA11 over-expressed GC cells, counterparts or alone,
cytokine array analyses of serum-free culture medium of HOXA11 over-expressed GC cells, we validated our findings through genetic manipulation of HMrSV5 cells and
neutralizing antibodies targeting
cytokines secreted by HOXA11 over-expressed GC cells in vitro, as well as utilized human peritoneal metastatic lesions to validate expression of potential targets. We identified that HOXA11 over-expressed GC cells strongly propelled mesothelial
fibrosis in vivo and in vitro, and HOXA11 regulated paracrine and autocrine of
PDGF BB and TGF β1 in GC cells to propel mesothelial
fibrosis. Meanwhile, HOXA11 over-expressed GC cells drove
PDGF BB and TGF β1 secretion to activate developmental-process related genes in HMrSV5 cells, including Egr1, which processes dependent on miR-181a-5p. Then, Egr1 could mediate peritoneal mesothelial
fibrosis. Correspondingly, Egr1 over-expressed HMrSV5 cells supported migration and peritoneal dissemination of GC cells. Together our results suggest that a feedforward amplifier circuity governing GC cells and mesothelial cells in peritoneum contribute to peritoneal
metastasis of GC cells.