Regulation of peritoneal metastasis of poorly differentiated gastric cancer by galectin-4 and the alteration of glycosylation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: The Noguchi Institute
• Principal Investigator: Ideo Hiroko 公益財団法人野口研究所, 研究部, 研究員 (90180322)
• Co-Investigator(Kenkyū-buntansha): 土田 明子 公益財団法人野口研究所, 研究部, 研究員 (70378024) ; 八須 和子 (広瀬和子) 公益財団法人野口研究所, 研究部, 研究員 (30625447)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ガレクチン-4 / 腹膜播種 / 転移 / 低分化型胃癌 / 糖鎖

Outline of Final Research Achievements

Suppression of galectin-4, which is highly expressed in poorly differentiated gastric cancer cells, by knockout (KO) or knockdown greatly reduced tumor formation in a mouse peritoneal seeding model. In correlation with the suppression of galectin-4 expression, proliferative capacity was decreased, and activated cMET, CD44, etc. were downregulated. Proximity ligation assay and proximity-dependent labeling revealed that these molecules and galectin-4 interact in close proximity to the cell membrane. Since this interaction was inhibited with the presence of galectin-4 inhibitory sugar or glycosylation inhibitor, glycans on the cells were analyzed by mass spectrometry. KO strain with reduced peritoneal seeding ability showed no change in N-linked glycans, while a large difference in the composition of neutral glycolipids was observed.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

転移・再発例に多く見られ胃がんの死亡率上昇の大きな原因である腹膜播種をおこす様な悪性度の高い癌に対する治療は未だ不十分である。本研究の様に糖鎖の変化と糖鎖認識分子の両方を調べる研究は他になく、従来の研究では見出しえなかった腹膜播種制御機構の一端を解明できた。単一タンパク質分子をターゲットとする場合と比べて、ガレクチン-4は糖鎖を介し多くの関連分子をコントロールする制御出来る点で有望であり、診断・治療標的分子としての可能性は少なくないと考えられる。