Reg IV enhances peritoneal metastasis in gastric carcinomas

Abstract

The role of Regenerating (Reg) IV on peritoneal metastasis was examined in gastric cancer using. Reg IV-transfected human gastric cancer cells (MKN28-R1, MKN28-R2, TMK1-R1), control transfectants (MKN28-R0, TMK1-R0), and REG4-knocked down MKN45 cells were examined in in vitro and in nude mice peritoneal metastasis models. Increase of expression and secretion of Reg IV, and levels of BCL-2, BCL-XL,survivin, phosphorylated AKT, and phosphorylated EGFR, and decrease of nitric oxide-induced apoptosis were found in Reg IV-transfectants, whereas those were abrogated in the knockdown cells. In mice models, increased number and size of peritoneal tumors and decreased apoptosis were found in Reg IV-transfectants, whereas those were abrogated by the knockdown cells. Mice survivals were worsened in Reg IV-transfectants-inoculated mice, but were improved in Reg IV-knockdown cell-inoculated mice. Levels of Reg IV protein in peritoneal lavage fluids increased in Reg IV-transfectants inoculated mice, but decreased in Reg IV-knockdown cell inoculated mice. In metastasized human gastric cancers, Reg IV positivity in peritoneum-metastasis cases was higher than those in negative cases. Reg IV was detected in peritoneal lavage fluids from human gastric cancer patients, in whose lavages keratin mRNA was detected by reverse transcriptase-polymerase chain reaction. Collectively, Reg IV might accelerate peritoneal metastasis in gastric cancer. Reg IV in lavage fluids might be a good marker for peritoneal metastasis.