Analysis of the mechanism leading treatment resistance by Mac-2bp through tumor associated macrophage in pancreatic cancer.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16441
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Suguru Mitsufuji 大阪大学, 医学系研究科, 招へい教員 (00828410)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 膵癌 / 腫瘍関連マクロファージ / 治療抵抗性 / Mac2-binding protein

Outline of Final Research Achievements

In this study, we focused on the effect of Mac2-binding protein (M2BP), which is clinically applied as a marker of liver fibrosis and reported to be upregulated in various types of cancers and associated with poor prognosis, on tumor-associated macrophages in pancreatic cancer. Immunohistochemistry of tumor-associated macrophages in resected pancreatic cancer specimens without preoperative therapy showed that M2BP expression coincided with CD206 expression, a marker of tumor-associated macrophages, suggesting that M2BP may induce tumor-associated macrophages. Evaluation of M2BP expression in the parental and gemcitabine-resistant pancreatic cancer cell lines showed that M2BP expression was higher in the gemcitabine-resistant line compared to the parental cell line.

Free Research Field

膵癌

Academic Significance and Societal Importance of the Research Achievements

浸潤性膵管癌（以下、膵癌）は、集学的治療の開発が積極的に進められているが、その治療成績は未だ十分なものとは言えず、癌の治療抵抗性に関わる機序解明および新規治療標的の開発が今後も必要とされている。本研究では様々な癌腫において発現の上昇しているM2BPが、膵癌において腫瘍の悪性度をもたらす腫瘍関連マクロファージを誘導する可能性を見出した。M2BPによる腫瘍関連マクロファージの誘導を抑制し、膵癌の治療抵抗性を制御することで、M2BPが新たな治療標的となり治療戦略の一助になり得ると考えている。