Induction by bombesin of peritoneal metastasis of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
BACKGROUND
We investigated the effect of the gastrointestinal regulatory peptide, bombesin, on the development of peritoneal metastasis from gastric cancers induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on Rho activity in the gastric cancers.


METHODS
Rats were allocated to three groups. All groups received MNNG (100 micrograms/ml) solution for 25 weeks from the start of the experiment. Group 1 (controls) received olive oil injections from the start of MNNG treatment; group 2 animals received alternate-day s.c. injections of bombesin (40 micrograms/kg body weight) in olive oil from the start of the experiment until the end of the experiment at week 52; and group 3 received the s.c. bombesin injection on alternate days from week 26 until week 52. The effect of bombesin on Rho activity in gastric cancer was examined by Western blotting.


RESULTS
Bombesin given from the start of the experiment (group 2) and after the MNNG treatment (group 3) both significantly increased the incidence of gastric cancer metastasis, compared with controls, at week 52: The incidence of metastasis was significantly higher in group 2 than in group 3. Bombesin from the start of the experiment (group 2) significantly increased the incidence of tumors with deeper invasion or more infiltrative growth pattern, or lymphatic vessel tumor invasion, while bombesin after MNNG treatment (group 3) significantly increased the incidence of lymphatic vessel invasion. Bombesin also increased the activity of Rho protein in the tumors.


CONCLUSIONS
Bombesin significantly increased the incidence of peritoneal metastasis from gastric cancers through the activation of Rho protein.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3, Nakamichi 1-chome, Higashinari-ku, Osaka 537-8511, Japan.
Iishi
H
H
Baba
M
M
Narahara
H
H
Uedo
N
N
Yano
H
H
Yamamoto
R
R
Mukai
M
M
Akedo
H
H
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002273:Carcinogens; D008297:Male; D008769:Methylnitronitrosoguanidine; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D020741:rho GTP-Binding Proteins; D001839:Bombesin