Development of a method to inhibit invasion of pancreatic cancer by controlling morphological changes of acinar cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20806
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyushu University
• Principal Investigator: KIBE Shin 九州大学, 医学研究院, 共同研究員 (00910605)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 膵癌 / 腫瘍微小環境 / 腫瘍浸潤 / 腺房-導管異形成(ADM) / 腫瘍関連マクロファージ(TAM) / 血管新生

Outline of Final Research Achievements

We have previously reported that acinar-to-ductal metaplasia (ADM)-like changes were observed in the invasive front of pancreatic cancer and that they were associated with tumor invasion. In this study, we observed that the density of angiogenesis was significantly abundant in ADM-like lesions at the invasive front of pancreatic cancer and which correlated with a poor prognosis. Furthermore, we detected that tumor-associated macrophages were increased in the ADM-like lesion at the invasive front areas. Especially, in these areas, MMP9-positive macrophages were high, which correlated with the areas of high angiogenic density.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

膵臓は周囲を主要な血管や他臓器に囲まれた臓器である。そのため、膵癌の唯一の根治治療は外科的切除であるが、半数以上の症例は診断時にすでに遠隔転移や局所進行のために切除の対象とはならず、膵癌は予後不良な疾患である。本研究では、膵癌の浸潤に際して腺房細胞のADM様変化が生じる部位の周囲微小環境において、腫瘍関連マクロファージがMMP9という分子を発現することが、血管新生増生に関与し、ひいては浸潤に関与する可能性を示唆した。このことは、膵癌の浸潤機序の解明の一助となる非常に意義のある結果である。