Molecular mechanisms for factors associated with perineural invasion as a prognostic factor in colorectal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21626
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Nozawa Hiroaki 東京大学, 医学部附属病院, 准教授 (80529173)
• Co-Investigator(Kenkyū-buntansha): 石原 聡一郎 東京大学, 医学部附属病院, 教授 (00376443) ; 川合 一茂 東京大学, 医学部附属病院, 届出研究員 (80571942) ; 園田 洋史 東京大学, 医学部附属病院, 助教 (80770205)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 大腸癌 / 神経周囲侵襲

Outline of Final Research Achievements

Perineural invasion is a prognostic factor in various solid tumors. Previous studies demonstrated that obstruction and stent insertion increase the frequency of perineural invasion (Pn) in colon cancer. In this study, we showed that obstructive colon cancer had a higher Pn rate at the oral side of than the anal side by histopathological examination. Stent placement increased Pn at both sides of obstructive cancer. The results support a hypothesis that mechanical stress may increase Pn locally. We considered that the above-mentioned phenomena might be imitated by stretch of cancer cells in vitro. One-dimension stretch induced transient phosphorylation of ERK, and later elevated expression in neutrophic factors such as BDNF and CTNF in several colon cancer cell-lines. Therefore, the activation of ERK signaling pathway may contribute to Pn in response to stress.

Free Research Field

腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

Pnが予後因子であることから、それを規定するneurotrophic factorやさらにその上流にあって発現を制御する分子を解明することで、新しい大腸癌に治療標的となりうる可能性がある。特に閉塞性大腸癌に対するステント留置は予後の観点からガイドライン上推奨されるレベルになっていないが、上記の標的治療を組み合わせることで予後が改善し推奨レベルにまで上がってくる可能性もある。治療選択肢が広がるという意味で多くの患者への恩恵につながると考えられる。