| Autor: |
Kawakubo, Masatomo, Komura, Hitomi, Goso, Yukinobu, Okumura, Motohiro, Sato, Yoshiko, Fujii, Chifumi, Miyashita, Masaki, Arisaka, Nobuhiko, Harumiya, Satoru, Yamanoi, Kazuhiro, Yamada, Shigenori, Kakuta, Shigeru, Kawashima, Hiroto, Fukuda, Michiko N., Fukuda, Minoru, Nakayama, Jun |
| Zdroj: |
Journal of Histochemistry and Cytochemistry; October 2019, Vol. 67 Issue: 10 p759-770, 12p |
| Abstrakt: |
Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt/Chst4double-knockout (DKO) mice by crossing A4gntknockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt/Chst4DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt/Chst4DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2, and Cxcr2transcripts in gastric mucosa of 5-week-old A4gnt/Chst4DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gntKO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt/Chst4DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, Cxcl1and Cxcr2were downregulated in A4gnt/Chst4DKO mice relative to age-matched A4gntKO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gntKO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2, and Cxcr2at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development: |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
