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Abstract​

We sought to visualize the migration of tumor-associated macrophages (TAMs) to tumor lesions and to evaluate the effects of anti-inflammatory drugs on TAM-modulated tumor progression in mice with colon cancer using a multimodal optical reporter gene system. Murine macrophage Raw264.7 cells expressing an enhanced firefly luciferase (Raw/effluc) and murine colon cancer CT26 cells coexpressing Rluc and mCherry (CT26/Rluc-mCherry, CT26/RM) were established. CT26/RM tumor-bearing mice received Raw/effluc via their tail veins, and combination of bioluminescence imaging (BLI) and fluorescence imaging (FLI) was conducted for in vivo imaging of TAMs migration and tumor progression. Dexamethasone (DEX), a potent anti-inflammatory drug, was administered intraperitoneally to tumor-bearing mice following the intravenous transfer of Raw/effluc cells. The migration of TAMs and tumor growth was monitored by serial FLI and BLI. The migration of Raw/effluc cells to tumor lesions was observed at day 1, and BLI signals were still distinct at tumor lesions on day 4. Localization of BLI signals from migrated Raw/effluc cells corresponded to that of FLI signals from CT26/RM tumors. In vivo FLI of tumors demonstrated enhanced tumor growth associated with macrophage migration to tumor lesions. Treatment with DEX inhibited the influx of Raw/effluc cells to tumor lesions and abolished the enhanced tumor growth associated with macrophage migration. These findings suggest that molecular imaging approach for TAM tracking is a valuable tool for evaluating the role of TAMs in the tumor microenvironment as well as for the development of new drugs to control TAM involvement in the modulation of tumor progression. 

Author information

Choi YJ1, Oh SG1, Singh TD1, Ha JH2, Kim DW3, Lee SW1, Jeong SY1, Ahn BC1, Lee J4, Jeon YH5.

1Department of Nuclear Medicine, Kyungpook National University, Daegu, Korea.

2Department of Pharmacology, Kyungpook National University, Daegu, Korea.

3Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea.

4Department of Nuclear Medicine, Kyungpook National University, Daegu, Korea; Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu, Korea. Electronic address: jaetae@knu.ac.kr.

5Department of Nuclear Medicine, Kyungpook National University, Daegu, Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea. Electronic address: jeon9014@gmail.com.