Elucidation of the mechanism that exosome derived from pancreatic cancer facilitate tumor progression mediated by TAM .

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16312
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tottori University
• Principal Investigator: MORIMOTO Masaki 鳥取大学, 医学部附属病院, 医員 (40808953)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 膵癌 / TAM / TYRO3 / エキソソーム

Outline of Final Research Achievements

In this study, we confirmed TYRO3 expression in five human PC cell lines (PANC-1, MIA PaCa-2, BxPC-3, AsPC-1, and PK-9). TYRO3 silencing and overexpression studies have revealed that TYRO3 promotes cell proliferation and invasion in PC via phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). Using a mouse xenograft model, we showed that tumor growth was significantly suppressed in mice subcutaneously inoculated with TYRO3-knockdown PC cells compared with mice inoculated with control PC cells. Furthermore, TYRO3 expression was examined in PC tissues obtained from 106 patients who underwent pancreatic resection for invasive ductal carcinoma through immunohistochemical staining. TYRO3-positive patients had poor prognoses for overall survival and disease-specific survival compared with TYRO3-negative patients. Multivariate analysis revealed that TYRO3 expression is an independent prognostic factor for overall survival.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、TAM familyに着目することで、難治癌である膵癌において新たな癌増殖のメカニズムの一端を示した。関連分子の研究をさらに進めることで、膵癌制御の臨床応用につながる可能性がある。