Functional intravital imaging of tumor-associated macrophages in tumor microenvironment

2016 Fiscal Year Final Research Report

• Project/Area Number: 26830070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kansai Medical University (2016); Kyoto University (2014-2015)
• Principal Investigator: KAMIOKA Yuji 関西医科大学, 医学部, 講師 (50511424)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 生体蛍光イメージング / FRET / 癌微小環境 / 好中球 / マクロファージ

Outline of Final Research Achievements

Tumor microenvironment (TME) consists of complex interactions between tumor cells and stroma cells. In this project, cellular behaviors and activity of ERK in TME of tumor-bearing mice were investigated by intravital Fluorescence Resonance Energy Transfer (FRET) imaging with two-photon excitation microscope. Initially, we focused on tumor associated macrophages (TAM) in TEM, however, neutrophils in TME showed more important relationship with tumor cells than TAM in our model. Our results showed that osteopontin secreted from 4T1 mouse breast tumor cell induced cell aggregation followed by ERK activation in neutrophils and neutrophil-specific cell death NETosis. In agreement with previous reports, NETosis inhibitor DNase I inhibited lung metastasis of 4T1 cells. These observations suggest that osteopontin promotes metastasis of 4T1 cells by activating neutrophils and inducing NETosis.

Free Research Field

細胞生物学、イメージング