Novel mechanism of acinar atrophy by pancreatic cancer microenvironment and its role in local invasion

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07943
• 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: Kyushu University
• Principal Investigator: SHIMAMOTO Masaya 九州大学, 大学病院, 助教 (00457433)
• Co-Investigator(Kenkyū-buntansha): 岩本 千佳 九州大学, 大学病院, 特任助教 (10752842) ; 鬼丸 学 九州大学, 医学研究院, 共同研究員 (80529876) ; 水元 一博 九州大学, 大学病院, 准教授 (90253418) ; 大内田 研宙 九州大学, 大学病院, 講師 (20452708)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膵癌 / 局所浸潤 / Acinar atrophy / 癌微小環境 / ADM

Outline of Final Research Achievements

In this study, we focused on the heterogeneity of the pancreatic cancer microenvironment and aimed to identify the cells responsible for inducing Acinar atrophy and to elucidate the mechanism in order to develop a new treatment for local invasion of pancreatic cancer. In the invasive front of human pancreatic cancer tissues, Acinar-to-ductal metaplasia (ADM)-like changes expressed TGFα were observed, and the expression of TGFα was associated with poor prognosis. Gene expression analysis also revealed phenotypic differences among cancer-associated ADM, sporadic ADM, and chronic pancreatitis ADM. These results suggest that the mechanism causing ADM varies depending on the tissue microenvironment and that cancer-associated ADM and acinar atrophy contribute to the invasion of pancreatic cancer cells into the parenchyma.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

膵癌進展を抑制するには、癌間質を含めた膵癌微小環境におけるheterogeneityを理解する必要があり、本研究によって癌関連ADMとAcinar atrophyが膵癌細胞の膵臓実質浸潤に寄与していることが示唆された。これまでに膵癌周囲微小環境としての膵腺房細胞の萎縮を誘導する責任細胞や因子に着目した報告はなく、これらの結果は膵癌局所浸潤におけるAcinar atrophyの機序の解明につながるものであり、それらの制御法の開発が新たな膵癌局所浸潤の治療法の開発に結び付くものと期待される。