Elucidation of sulfomucin-mediated gastric carcinogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04712
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Shinshu University
• Principal Investigator: Nakayama Jun 信州大学, 学術研究院医学系, 教授 (10221459)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 胃粘液 / 硫酸化糖鎖 / 糖転移酵素 / 硫酸転移酵素 / ダブルノックアウトマウス / 粘膜下異所性腺

Outline of Final Research Achievements

Sulfomucin (SuM) is sulfated O-glycan attached to specific scaffold proteins. In order to elucidate the role of SuM in gastric cancer development, we generated A4gnt/Chst4 double-knockout (DKO) mice by crossing A4gnt knockout mice that spontaneously develop differentiated-type gastric adenocarcinoma and Chst4 knockout mice that are defective in the sulfotransferase, GlcNAc6ST-2. A4gnt/Chst4 DKO mice developed differentiated-type gastric adenocarcinoma as they aged alike A4gnt KO mice. However, gastric erosion took place in A4gnt/Chst4 DKO mice as early as 3-weeks of age, and these lesions were eventually taken over by gastritis cystica profunca (GCP). In human early differentiated-type gastric adenocarcinoma, GCP was significantly associated with adenocarcinoma without SuM production than adenocarcinoma with SuM production. These results combined together indicate that SuM played essential role in preventing GCP in adenocarcioma but a minor role in gastric cancer progression.

Free Research Field

人体病理学、糖鎖生物学、組織細胞化学