Basic study for the development of PET diagnosis specific for CD44 variant-positive gastric cancer stem like cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293178
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: Suzuki Hidekazu 慶應義塾大学, 医学部, 教授 (70255454)
• Co-Investigator(Kenkyū-buntansha): INOUE HIROYOSHI 慶應義塾大学, 医学部, 教授 (10213175) ; MURAKAMI KOUJI 慶應義塾大学, 医学部, 教授 (50200267) ; SHIBATA SHINSUKE 慶應義塾大学, 医学部, 講師 (70407089)
• Co-Investigator(Renkei-kenkyūsha): SAYA HIDEYUKI 慶應義塾大学, 医学部, 教授 (80264282)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: CD44v9 / グルタチオン / 酸化ストレス / シスチントランスポーター / 胃癌幹細胞 / trastuzumab

Outline of Final Research Achievements

1)CD44v9-MKN28 cells were more resistant to 5-FU than CD44s-MKN28. With sulfasalazine, 5-FU enhanced ROS and reduced GSH even in CD44v9-MKN28, suggesting an importance of CD44v9 for 5-FU resistance. 2)Hp exposure significantly enhanced migration of CD44v9-MKN28, indicating that CagA accumulation by autophagy inhibition would accelerate tumor infiltration. 3)Trastuzumab significantly enhanced intramitochondrial MnSOD with the increase of GSH in CD44v9-NCI-N87 cells as compared to NCI-N87. 4)In xenografts, although 5-FU reduced tumor volume of CD44s-MKN28, no reduction of CD44v9-MKN28 was shown. With sulfasalazine, 5-FU significantly reduced tumor volume of CD44v9-MKN28, possibly by inhibiting CD44v9-xCT system, suggesting of xCT as a potential target of CD44v9 (+) cancer stem-like cells. (5)Hp infection expanded xenograft tumor of MNK28-CD44v9 compared to non-infected MNK28-CD44v9 or infected MKN28-CD44s, suggesting the high proliferative activity under CagA accumulation.

Free Research Field

消化器内科学