Embryonic basal cells at squamous columnar junction as the cells of origin for Barrett esophagus

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24058
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Terayama Masayoshi 国立研究開発法人国立国際医療研究センター, その他部局等, 外科 レジデント (20843014)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: バレット食道 / 組織幹細胞 / 食道胃接合部

Outline of Final Research Achievements

We immunologically examined the expression of Glutathione S-transferase Omega 2 (GSTO2), normally expressed in the nethermost cells of esophageal mucosa, and found GSTO2-positive cell population in glands of esophago-gastric junctions. Immuno-histochemical staining of 87 resected specimens by esophagectomy revealed that GSTO2 expressed in 13 of 27 (48%) esophageal adenocarcinoma (EAC) cases and 13 of 62 (21%) esophageal squamous cell carcinoma (ESCC) cases, respectively. To examine the function of GSTO2 in ESCC and EAC, we prepared stable GSTO2-transfected and mock-transfected cells which possessing empty vector. Forced expression of GSTO2 inhibited tumor cell growth and suppressed the membrane expression of E-cadherin, a marked epithelial marker, in ESCC but did not affect EAC cell functions. These results suggest that GSTO2 may have different roles in carcinogenesis between ESCC and EAC.

Free Research Field

食道

Academic Significance and Societal Importance of the Research Achievements

バレット食道は食道腺癌の発生母地として知られるが、バレット食道の発生起源とされる”胚性上皮細胞”の挙動と機能的変化については、特異的分子マーカーの同定に至らず、解明が進んでいない。本研究の学術的・社会的意義は、”胚性上皮細胞”に限局して発現し、腺癌発症に相関している分子を同定したことである。更に、本分子の発現制御機構並びに分子機能は食道扁平上皮と腺上皮で異なることを明らかにしており、食道扁平上皮が腺上皮へと置き換わるバレット食道の分子病態解明に繋がる、重要な知見が得られた。