title: Contribution of resident and recruited macrophages to the photodynamic intervention of colorectal tumor microenvironment.
abstract: 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-α). 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.
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina.
authors.forename: María Florencia
authors.identifier: http://orcid.org/0000-0002-0300-6606
authors.initials: MF
authors.lastname: Pansa
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina.
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Lamberti
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina.
authors.forename: Ingrid Sol
authors.initials: IS
authors.lastname: Cogno
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Silvia Graciela
authors.initials: SG
authors.lastname: Correa
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina.
authors.forename: Natalia Belén
authors.initials: NB
authors.lastname: Rumie Vittar
authors.affiliation: Departamento de Biología Molecular, Facultad de Ciencias Exactas Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, 5800, Río Cuarto, Córdoba, Argentina. vrivarola@exa.unrc.edu.ar.
authors.forename: Viviana Alicia
authors.initials: VA
authors.lastname: Rivarola
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D001119:Arginase / Q000737:chemistry; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D017077:Culture Media, Conditioned / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D021621:Imaging, Three-Dimensional; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry; D018874:Spheroids, Cellular / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D017319:Photosensitizing Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001119:Arginase
keywords: Colorectal cancer; Macrophages; Photodynamic therapy; TAMs; Tumor microenvironment