Journal
TUMOR BIOLOGY
Volume 37, Issue 1, Pages 541-552Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-3768-5
Keywords
Photodynamic therapy; Tumor microenvironment; Macrophages; TAMs; Colorectal cancer
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Funding
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
- Agencia Nacional de Promocion Cientifica y Tecnologica (PICT)
- Secretaria de Ciencia y Tecnica (SECyT)
- Universidad Nacional de Rio Cuarto, Argentina
- CONICET
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The study of cellular interactions in the tumor microenvironment has become one of the main areas of research in the fight against cancer. Tumor-associated macrophages (TAMs) influence tumor progression and therapy response due to its functional plasticity. Regarding cancer treatment, photodynamic therapy (PDT) is a minimally invasive and clinically approved procedure that involves the administration of a photosensitizer (PS), a nontoxic photosensitizing drug which is selectively retained in neoplastic tissue. Here, we investigated the role of resident and nonresident macrophages in the context of a PDT-treated colorectal tumor by developing a combination of 2-D and three-dimensional (3-D) experimental platform, recreating tumor-stroma interactions in vitro. Enhancement of cytotoxicity of PDT was achieved in the presence of nonresident macrophages which had a strong anti-tumor phenotype mediated by the production of nitric oxide, IL-6, and tumor necrosis factor alpha (TNF-alpha). On the contrary, tumor resident macrophages induced a pro-tumor phenotype promoting tumor cell migration and endothelial stimulation. Due to their plasticity, tumor-resident or tumor-recruited macrophages can differentially influence the response of tumors to PDT, so their multifactorial roles should be considered in the overall design of anti-tumor therapeutic.
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