Pathobiology of Gastric Carcinoids and Adenocarcinomas in Rodent Models and Patients: Studies of Gastrocystoplasty, Gender-Related Factors and Autophagy

摘要

A series of studies of both carcinoids (ECLoma) and adenocarcinomas in both rodent models and patients has been performed to investigate several factors influencing gastric tumorigenesis. ECL cell hyperplasia and ECLoma occurred in the segment of oxyntic mucosa six months after gastrocystoplasty with fundectomy in rats. Gastric ECL cell hyperplasia and ECLoma develop after one year in rats treated with omeprazole or 2-4 months in Mastomys treated with loxtidine.The ECL cells were fully under control of gastrin during pregnancy and lactation, and during the estrous cycle. Estrogen-like agents (dieldrin and/or toxaphene treatment for 9 months) did not induce any changes in the gastrin-ECL cell axis neither in female nor male rats. Ultrastructure of ECL cells in Mastomys displayed impaired formations of vacuoles and lipofuscin bodies (biomarkers of autophagic pathway), which was associated with weak immunostaining of ATG-5 and ATG-16. A similar immunostaining feature was observed in carcinoids patients. Spontaneous adenocarcinomas in oth hypergastrinemic cotton rats and INS-GAS mice, and patients showed also weak immunostaining of ATG-5 and ATG-16. Taken together, the results of these studies suggest an impaired autophagy (mainly formation of ATG-5-ATG-12-ATG-16 complex) in gastric carcinoids of Mastomys and patients as well as in gastric adenocarcinomas of cotton rats, INS-GAS mice and patients.