Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis.

Abstract

Dendritic cell appearance and differentiation during early and late stages of rat stomach carcinogenesis were studied in the pyloric mucosa. Young male rats were given drinking water with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; 100 mg/liter) for 14 days. Use of competitive RT-PCR and northern blotting showed that MNNG exposure induced 3- to 4-fold greater expression of the genes for integrin beta7 and integrin alphaE2 (identical with antigen OX-62, a dendritic cell marker), as well as three cytokines, IL-4, GM-CSF and TNFalpha, in the stomach pyloric mucosa of resistant Buffalo rats compared to sensitive ACI rats. These genes were minimally expressed in control animals. The results confirm the appearance of dendritic cells in the target pyloric mucosa and suggest the possibility that dendritic cell differentiation and maturation are induced by various cytokines, at least in Buffalo rats. Competitive RT-PCR showed expression of integrin alphaE2 and beta7, MHC class II-associated invariant chain (Ii), MHC class II, B7-1, CD28, GM-CSF and TNFalpha genes in all 12 examined stomach adenocarcinomas and adenomas induced in male Lewis and WKY rats with 30 weeks' MNNG exposure, suggesting the presence of dendritic cells in tumors. OX-62 staining and western blotting for OX-62 also confirmed the presence of dendritic cells in tumors. However, the population of dendritic cells in tumors was less than that in the pyloric mucosa after 14 days' MNNG exposure. The present results suggest that immune defense involving dendritic cells is marshaled from the very early initiation stage during rat stomach cancer development, but is downgraded in developed tumors.

• Authors: Motoi Takeuchi, Masami Yamamoto, Masae Tatematsu, Kazumasa Miki, Yoshiyuki Sakaki, Chie Furihata
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 93 Issue 8 Pg. 925-34 (Aug 2002) ISSN: 0910-5050 [Print] Japan
• PMID: 12716471 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Cadherins
• Carcinogens
• Integrin alpha Chains
• Integrin beta Chains
• Tumor Necrosis Factor-alpha
• alpha E integrins
• integrin beta7
• Methylnitronitrosoguanidine
• Interleukin-4
• RNA
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Antigens, CD (biosynthesis)
• Binding, Competitive
• Blotting, Northern
• Blotting, Western
• Cadherins (biosynthesis)
• Carcinogens
• Cell Differentiation
• Dendritic Cells (pathology)
• Gastric Mucosa (pathology)
• Granulocyte-Macrophage Colony-Stimulating Factor (biosynthesis)
• Immunohistochemistry
• Integrin alpha Chains (biosynthesis)
• Integrin beta Chains (biosynthesis)
• Interleukin-4 (biosynthesis)
• Male
• Methylnitronitrosoguanidine
• RNA (metabolism)
• Rats
• Rats, Inbred Lew
• Rats, Inbred WKY
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (pathology)
• Tumor Necrosis Factor-alpha (biosynthesis)