Function of mesenchymal myofibroblast to sustain gastrointestinal stemness and niche factors for epithelial differentiation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19359
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: KATANO Takahito 名古屋市立大学, 大学院医学研究科, 研究員 (50768372)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 幹細胞 / mesenchymal cell / 大腸腫瘍

Outline of Final Research Achievements

Stem cells are influenced by a microenvironmental niche that includes mesenchymal cells. A gastric mesenchymal myofibroblast (GMF) and intestinal mesenchymal myofibroblast (IMF) cell line were established from mouse. Real-time quantitative RT-PCR showed that Gas1 expression was higher in GMFs, and Hoxc8, Notch1, and Sox10 expression was higher in IMFs.
We analyzed 105 colorectal laterally spreading tumors (LSTs) resected by endoscopic submucosal dissection and investigated clinicopathological differences among LST subtypes to identify factors indicative of malignant transformation and invasion. Ectopic gastric and intestinal phenotypes, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade in colorectal LSTs, and these markers are correlated with early tumor progression in each LST subtype.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

正常状態のみならず発癌プロセスにおいて細胞外環境が消化管幹細胞の挙動に及ぼす影響や幹細胞の可塑性がどう媒介されるかは未解明な点が多い。本研究で胃腸腺管におけるニッチとしての筋線維芽細胞にも組織特異性の存在が示唆され、消化管上皮の組織恒常性維持機構、発癌のメカニズムの解明にもつながるものである。異所性の胃型・腸型形質発現，内分泌細胞分化，SOX2発現が側方発育型大腸腫瘍の早期の発癌・進展過程における悪性化・粘膜下層浸潤の予測マーカーとなり得ることを見出したが、癌幹細胞の胃型・腸型発現の制御機構には類似点が多いと考えられ、癌細胞における新たな治療戦略の礎になるものと考えられる。