The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP- 1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma
Autor: | Vincenzo Gigantino, Giuseppe Portella, Gianni Marone, Viviana Vastolo, Renato Franco, Francesco Borriello, Eloise Scamardella, Sarah Di Somma, Carmela Passaro |
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Přispěvatelé: | Passaro, Carmela, Borriello, Francesco, Vastolo, Viviana, Di Somma, Sarah, Scamardella, Eloise, Gigantino, Vincenzo, Franco, Renato, Marone, Gianni, Portella, Giuseppe, Somma, Sarah Di |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Time Factors Monocyte chemotaxis Angiogenesis medicine.medical_treatment Cell Plasticity Thyroid Carcinoma Anaplastic 0302 clinical medicine Tumor-associated macrophage Cancer immunotherapy Tumor Microenvironment Medicine Promoter Regions Genetic Chemokine CCL2 Oncolytic Virotherapy Innate immunity Neovascularization Pathologic tumor-associated macrophages Chemotaxis Gene Expression Regulation Neoplastic Oncolytic Viruses Phenotype Oncology Chemokine 030220 oncology & carcinogenesis Host-Pathogen Interactions Female Research Paper Oncolytic adenovirus Down-Regulation Mice Nude Transfection Adenoviridae 03 medical and health sciences Tumor vasculature Cell Line Tumor Animals Humans Interleukin 8 Thyroid Neoplasms Virotherapy Tumor microenvironment Binding Sites business.industry Macrophages Interleukin-8 Transcription Factor RelA Xenograft Model Antitumor Assays Oncolytic virus 030104 developmental biology Immunology Cancer research business |
Zdroj: | Oncotarget |
Popis: | Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy. |
Databáze: | OpenAIRE |
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