Molecular dissection of angiogenesis in colorectal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Yamamoto Eiichiro 札幌医科大学, 医学部, 訪問研究員 (60567915)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大腸がん / 微小環境

Outline of Final Research Achievements

We detected frequent upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in TECs. Immunohistochemistry revealed that AEBP1 is upregulated TECs and cancer stromal cells. Levels of AEBP1 expression in human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct co-culture with CRC cells. AEBP1 knockdown suppressed proliferation, migration and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 may promote angiogenesis through regulating those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target.

Free Research Field

消化器病

Academic Significance and Societal Importance of the Research Achievements

腫瘍間質は、がん関連線維芽細胞、腫瘍血管内皮細胞(tumor endothelial cell, TEC)、種々の免疫細胞などから構成されている。腫瘍間質細胞はがんの増殖、浸潤および転移に有利な微小環境を構築することから、その制御は重要な治療戦略である。本研究でAEBP1 (adipocyte enhancer-binding protein 1) がTECで高発現し、血管新生を促進すること、そしてAEBP1の阻害が腫瘍血管新生を抑制しうることを明らかとしており、今後がん微小環境におけるAEBP1の機能を解明することで、新たな分子標的治療法の開発につなげることができると考えられた。