title: Influence of tumor cell culture supernatants on macrophage functional polarization: in vitro models of macrophage-tumor environment interaction.
abstract: OBJECTIVE
  Macrophages are heterogeneous cells with extensive functional plasticity; they can change their functional profiles repeatedly in response to environmental changes anywhere between their extreme phenotypical programs (labeled as M1 and M2 polarization, respectively). In terms of antitumoral immune response, M1 macrophages are considered to be beneficial, while M2 macrophages supposedly promote tumor progression. Tumor-associated macrophages (TAMs) represent a major leukocyte population present in many tumors. Although many studies indicate that TAMs elicit several M2-associated protumoral functions, including promotion of angiogenesis, matrix remodeling and suppression of adaptive immunity, their role regarding tumor progression is still controversial. The aim of the present study was to develop an appropriate in vitro model to study the effect of tumor-secreted soluble factors on the functional phenotype of macrophages.
  
  
  METHODS
  THP-1 human monocytic line cells and peripheral blood mononuclear cells from healthy volunteers were used for macrophage differentiation; primary tumor cell culture supernatants or tumor cell line supernatants were employed along with various cytokines, growth factors and other stimuli to design different model variants and to better mimic the in vivo tumor microenvironment.
  
  
  RESULTS
  The cytokine secretion patterns of these macrophages suggest that primary tumor cell culture supernatants are able to switch the macrophage phenotype or to induce functional polarization of macrophages toward a mixed M1/M2 phenotype. Conclusions. These data support the hypothesis that TAM behavior is modulated by the tumor microenvironment itself.
authors.affiliation: Infection and Immunity Laboratory, National Institute for Research and Development in Microbiology and Immunology Cantacuzino, 103 Spl Independentei, sector 5, 050096 Bucharest, Romania.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Caras
authors.forename: Catalin
authors.initials: C
authors.lastname: Tucureanu
authors.forename: Lucian
authors.initials: L
authors.lastname: Lerescu
authors.forename: Ramona
authors.initials: R
authors.lastname: Pitica
authors.forename: Laura
authors.initials: L
authors.lastname: Melinceanu
authors.forename: Stefan
authors.initials: S
authors.lastname: Neagu
authors.forename: Aurora
authors.initials: A
authors.lastname: Salageanu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000473:pathology*; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D018664:Interleukin-12; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor