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Published on: June 16, 2018
Ionizing Radiation-Induced Tumor Cell-Derived Microparticles Prevent Lung Metastasis by Remodeling the Pulmonary
Danyi Zhai1, Jing Huang1, Yan Hu1
1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Purpose:
The majority of cancer-related deaths are attributed to metastasis rather than localized primary tumor progression. However, the factors that regulate the premetastatic niche (PMN) and metastasis have not yet been clearly elucidated. We investigated the antimetastatic effects of irradiated tumor cell-derived microparticles (RT-MPs) and highlighted the role of innate immune cells in PMN formation.
Methods And Materials:
Mice were treated 3 times with isolated RT-MPs, followed by tumor cell injection via the tail vein. The hematoxylin and eosin staining was performed to assess the number of tumor nodules in the lungs, and in vivo luciferase-based noninvasive bioluminescence imaging was conducted to detected tumor burden. The mechanisms of RT-MPs mediated PMN formation was evaluated using flow cytometry, transwell assay, and reverse transcription-polymerase chain reaction.
Results:
RT-MPs inhibited tumor cell colonization in the lungs. Neutrophils phagocytosed RT-MPs and secreted CCL3 and CCL4, which induced monocytes chemotaxis and maturation into macrophages. RT-MPs promoted the transition of neutrophils and macrophages into antitumor phenotypes, hence inhibiting cancer cell colonization and proliferation.
Conclusions:
RT-MPs inhibited PMN formation and lung metastasis in a neutrophil- and macrophage-dependent but T cell-independent manner.
Insights
Irradiated tumor cell-derived microparticles (RT-MPs) prevent cancer metastasis by reprogramming immune cells. RT-MPs inhibit premetastatic niche formation, reducing tumor colonization in the lungs.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis Research
Background:
- Cancer metastasis, not primary tumors, causes most cancer deaths.
- Understanding premetastatic niche (PMN) formation is crucial for developing antimetastatic therapies.
- The precise regulators of PMN development and metastasis remain incompletely understood.
Purpose of the Study:
- To investigate the antimetastatic effects of irradiated tumor cell-derived microparticles (RT-MPs).
- To elucidate the role of innate immune cells in the regulation of PMN formation by RT-MPs.
Main Methods:
- Mice received RT-MP treatments before tumor cell injection.
- Lung metastasis was quantified using hematoxylin and eosin staining and bioluminescence imaging.
- Immune cell involvement was assessed via flow cytometry, transwell assays, and RT-PCR.
Main Results:
- RT-MPs significantly inhibited tumor cell colonization in the lungs.
- Neutrophils, after phagocytosing RT-MPs, secreted chemokines (CCL3, CCL4) attracting monocytes.
- RT-MPs induced neutrophils and macrophages to adopt antitumor phenotypes, suppressing cancer cell growth.
Conclusions:
- RT-MPs effectively inhibit premetastatic niche formation and lung metastasis.
- The antimetastatic effect is dependent on neutrophils and macrophages.
- The mechanism is independent of T cells.
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