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Published on: May 6, 2018
Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model
1State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, PR China.
Abstract:
Previous research to investigate the interaction between malaria infection and tumor progression has revealed that malaria infection can potentiate host immune response against tumor in tumor-bearing mice. Exosomes may play key roles in disseminating pathogenic host-derived molecules during infection because several studies have shown the involvement and roles of extracellular vesicles in cell-cell communication. However, the role of exosomes generated during Plasmodium infection in tumor growth, progression and angiogenesis has not been studied either in animals or in the clinics. To test this hypothesis, we designed an animal model to generate and isolate exosomes from mice which were subsequently used to treat the tumor. Intra-tumor injection of exosomes derived from the plasma of Plasmodium-infected mice provided significantly reduced Lewis lung cancer growth in mice. We further co-cultured the isolated exosomes with endothelial cells and observed significantly reduced expression of VEGFR2 and migration in the endothelial cells. Interestingly, high level of micro-RNA (miRNA) 16/322/497/17 was detected in the exosomes derived from the plasma of mice infected with Plasmodium compared with those from control mice. We observed that overexpression of the miRNA 16/322/497/17 in endothelial cell corresponded with decreased expression of VEGFR2, inhibition of angiogenesis and inhibition of the miRNA 16/322/497/17 significantly alleviated these effects. These data provide novel scientific evidence of the interaction between Plasmodium infection and lung cancer growth and angiogenesis.
Insights
Malaria infection generates exosomes that inhibit lung cancer growth and angiogenesis. These exosomes, containing specific microRNAs, reduce tumor progression by targeting endothelial cells and VEGFR2 expression.
Area of Science:
- Oncology
- Immunology
- Parasitology
Background:
- Previous studies suggest malaria infection can enhance anti-tumor immunity.
- Exosomes, involved in cell communication, may mediate host responses during infection.
- The role of Plasmodium-derived exosomes in tumor growth and angiogenesis remains unexplored.
Purpose of the Study:
- To investigate the effect of exosomes from Plasmodium-infected mice on lung cancer growth and angiogenesis.
- To identify molecular mechanisms underlying this interaction.
Main Methods:
- Generated exosomes from Plasmodium-infected mice plasma.
- Administered exosomes via intra-tumor injection in a Lewis lung cancer mouse model.
- Co-cultured exosomes with endothelial cells and analyzed VEGFR2 expression and cell migration.
- Quantified microRNA levels in exosomes using molecular techniques.
Main Results:
- Exosomes from infected mice significantly reduced Lewis lung cancer growth.
- These exosomes decreased VEGFR2 expression and endothelial cell migration.
- Elevated levels of specific microRNAs (16/322/497/17) were found in exosomes from infected mice.
- Overexpression of these microRNAs in endothelial cells mimicked the anti-angiogenic effects.
Conclusions:
- Exosomes derived from Plasmodium infection possess anti-tumor properties against lung cancer.
- Specific microRNAs within these exosomes play a crucial role in inhibiting angiogenesis by downregulating VEGFR2.
- This study reveals a novel interaction between malaria infection and lung cancer progression.

