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Low-frequency ultrasound-induced VEGF suppression and synergy with dendritic cell-mediated anti-tumor immunity in murine prostate cancer cells in vitro
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation. DCs from the bone marrow of BALB/c mice were stimulated by the addition of cytokines (granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4)), and we analyzed their proliferation status via flow cytometric recognition of the surface antigen markers CD11c and CD83. The results demonstrated that co-culture with RM-1 cells markedly inhibited expression of the general marker CD11c and the mature marker CD83; UM weakened this inhibition by down-regulating VEGF expression. T lymphocytes were extracted from murine spleens, and CD4 and CD8a were identified as the biomarkers of activated cells participating in the anti-tumor immune response. When DCs, T lymphocytes and RM-1 cells were co-cultured, cell migration and invasion assays and cytoactive detection showed that UM could not only directly suppress PCa cell evolution but also promote activation of anti-tumor immunocytes in the VEGF-inhibited microenvironment.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
0301 basic medicine
T-Lymphocytes
Science
Contrast Media
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Antigen
Cell Movement
Cell Line, Tumor
Animals
Medicine
Ultrasonics
Cell Proliferation
Mice, Inbred BALB C
Microbubbles
Multidisciplinary
Cell growth
business.industry
Prostatic Neoplasms
Cell migration
Dendritic Cells
Dendritic cell
Coculture Techniques
Vascular endothelial growth factor
Vascular endothelial growth factor A
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Immunology
Cancer research
Bone marrow
business
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....68329a43330115862dbfc48233d45f3f