Elucidation of the mechanism of colorectal cancer-associated fibroblasts to promote cancer malignancy and treatment resistance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Juntendo University
• Principal Investigator: tomoyoshi shibuya 順天堂大学, 医学部, 先任准教授 (60365616)
• Co-Investigator(Kenkyū-buntansha): 折茂 彰 順天堂大学, 大学院医学研究科, 教授 (70275866)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 癌微小環境 / 線維芽細胞 / 浸潤・転移

Outline of Final Research Achievements

We collected specimens from colon cancerous and non-cancerous areas resected by surgery, and successfully established 21 cases of CAFs and control fibroblasts. We also established 8 colon cancer organoids. Immunohistochemical staining using a cell-specific antibody confirmed the establishment of highly pure fibroblasts. In addition, RNA-sequencing identified multiple genes that were significantly upregulated in CAFs compared to non-cancerous control fibroblasts. In the future, we will establish a 3D colon cancer organoid culture, establish a co-culture system of CAFs and colon cancer organoids, prepare a PDX model by orthotopic co-transplantation into mice, and conduct biological research on cancer invasion and metastasis induced by CAFs.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

難治性大腸癌の転移再発に対する現行の抗癌剤の治療効果は不十分であり、根治的治療の開発が望まれている。大腸癌の間質に多く存在する線維芽細胞は癌浸潤、転移や治療抵抗性獲得に関与していることが知られているが、その分子機構の理解は不十分である。本研究は、大腸癌由来線維芽細胞を抽出し、大腸癌の浸潤、転移や治療抵抗性獲得に与える影響を分子レベルで解明することにより癌悪性化機構の理解を深める意義がある。