Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts.
Wada K. Sakamoto C. Matsuda K. Uchida T. Noguchi H. Mizuno H. Akamatsu T. Kasuga M.
The Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
To investigate whether gastric epithelial cells secrete growth factors involved in stromal cell growth, we examined the effects of conditioned media obtained from gastric cancer cells on murine BALB/c 3T3 cells and primary cultured human gastric fibroblasts. Conditioned media from MKN-1 gastric cancer cells were applied to a heparin-affinity column. The fraction eluted from the column at 0.4 M NaCl stimulated DNA synthesis and phosphorylation of PDGF alpha-receptors on tyrosine in BALB/c 3T3 cells. The fraction-induced stimulation of DNA synthesis in gastric fibroblasts was more marked than in BALB/c 3T3 cells. However, the fraction failed to stimulate DNA synthesis in CHO-ER cells overexpressing EGF receptors and phosphorylation of PDGF beta-receptors on tyrosine in BALB/c 3T3 cells. Immunoblot analysis of the media confirmed that PDGF-AA-like peptides are released from gastric cancer cells, immortalized gastric epithelial cells, and primary cultured gastric epithelial cells. Anti-PDGF neutralizing antibodies produced only a partial inhibition of 0.4 M NaCl fraction-induced enhanced DNA synthesis. Thus, in addition to PDGF-AA peptide, other bioactive substance(s) are probably released from MKN-1 gastric cancer cells. Our results suggest that gastric epithelial cells secrete PDGF-AA-like peptides responsible for stromal cell growth through paracrine mechanisms.
Mediterranean epidemiological evidence on tomatoes and the prevention of digestive-tract cancers.
La Vecchia C.
Istituto di Ricerche Farmacologiche Mario Negri, Universita degli Studi di Milano, Milan, Italy.
Tomatoes have been estimated as the second most important source of vitamin C, after oranges, in an Italian population. We have therefore considered the relationship between tomato intake and the risk of digestive tract cancers using data from a series of case-control studies conducted in Italy between 1983 and 1992, and including 317 histologically confirmed, incident cases of cancer of the oral cavity and pharynx, 85 of the esophagus, 723 of the stomach, 955 of the colon, and 629 of the rectum, and a total of 2879 controls admitted for acute, non-neoplastic conditions, unrelated to long-term modifications of diet. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for subsequent quartiles of intake of tomatoes were derived, after allowance for age, sex, study center, education, smoking, alcohol drinking, and total calorie intake. There was a consistent pattern of protection for all sites. The ORs for the highest consumption quartile were 0.65 (95% CI 0.4-1.0) for oral cavity, pharynx, and esophagus, 0.43 (95% CI 0.3-0.6) for stomach, 0.39 (95% CI 0.3-0.5) for colon, and 0.42 (95% CI 0.3-0.6) for rectum. Another study of colorectal cancer, based on 1,953 cases and 4,154 controls, conducted between 1992 and 1996 and using a more detailed food frequency questionnaire, confirmed that tomato intake was significantly protective on colorectal cancer risk, even after allowance for several potential confounding factors, including measures of body mass index, calorie intake, and physical activity. The ORs for the highest consumption quintile were 0.79 (95% CI 0.6-0.9) for colon, and 0.71 (95% CI 0.5-0.9) for rectal cancer. The beneficial effect of tomatoes observed in these epidemiological studies may be due to the fact that they constitute one of the most specific features of the Mediterranean diet. This has both a scientific and a public health relevance.