Accumulated evidence suggests that a functional loop composed of
gastrin and
cholecystokinin B receptor (CCK-BR) may exist in gastric
carcinogenesis. However, this suggestion is not completely supported due to a lack of direct evidence, and the underlying mechanism is not completely understood. Here, we evaluated the effects of
gastrin/CCK-BR signaling on the cell growth, invasion, and expression of MMP-2 and
VEGF, as well as xenograft growth in vivo. Furthermore, we detected
gastrin mRNA content in human
gastric cancer tissues, metastatic lymph nodes, and adjacent nontumor tissues. We found that the forced
gastrin could promote the proliferation, migration, and invasion of
gastric cancer cells by upregulating the expression of MMP-2 and
VEGF. Blocking
gastrin/CCK-BR signal using either
Proglumide, a CCK-BR antagonist, or
shRNA against
GASTRIN significantly inhibited the
gastrin-promoting effects. In vivo study revealed that the
tumor growth in nude mice inoculated with
gastrin-overexpressed cells was significantly faster than control cells. The
gastrin mRNA content in metastatic lymph nodes was higher in patients with
gastric cancer than in primary
gastric cancer and adjacent nontumor tissues. In conclusion, we provided direct evidence and possible mechanism of
gastrin/CCK-BR signaling in the initiation and progression of
gastric cancer.