2022 Fiscal Year Final Research Report
Elucidation of the mechanism of colorectal cancer progression regulated by cancer-associated fibroblasts through TIMPs and its clinical application
Project/Area Number |
19K18159
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Nagoya City University |
Principal Investigator |
Nakai Nozomu 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50811717)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 癌関連線維芽細胞 / CAFs / 大腸癌 / TIMP-1 / 遊走 / 転移 / 共培養 |
Outline of Final Research Achievements |
Cancer-associated fibroblasts (CAFs) and cancer cells interact to promote tumor progression, including metastasis. The tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to promote cancer cell migration, which is contradictory to its role as an inhibitor of matrix metalloproteinase. In this study, researchers investigated the effect of TIMP-1 on colon cancer cell migration and identified its primary source. The results showed that TIMP-1 promotes the migration of LoVo colon cancer cells and that CAFs are the primary source of TIMP-1. Additionally, TIMP-1 secretion was higher in CAFs co-cultured with cancer cells than in monocultured CAFs, indicating that TIMP-1 production is enhanced through cancer-stromal interaction. The study suggests that the interaction between cancer cells and CAFs in the tumor microenvironment promotes cancer cell migration by increasing TIMP-1 production.
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Free Research Field |
大腸癌
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Academic Significance and Societal Importance of the Research Achievements |
この研究は大腸癌の病態生理や治療法の開発に対して示唆を与える可能性がある。具体的には、癌関連線維芽細胞(CAFs)が大腸癌細胞の遊走に影響を与えるメカニズムを解明することができ、がんの進行や転移を抑制する新しい治療法の開発に役立つ可能性がある。よって、癌細胞を取り囲む腫瘍微小環境に対する治療アプローチが提唱されうる。 社会的に、大腸癌は世界中で非常に高頻度の悪性腫瘍であり治療法開発は常に課題であり、この研究により大腸癌の病態生理に対する理解が深まり、適切な治療法の開発に寄与することが期待される。また癌治療において、細胞外マトリックスに対する治療法の開発が進む可能性もある。
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