title: Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) has a central role in cancer progression and metastatic dissemination and may be induced by local inflammation. We asked whether the inflammation-induced acquisition of mesenchymal phenotype by neoplastic epithelial cells is associated with the onset of mesenchymal stromal cell-like immune-regulatory properties that may enhance tumour immune escape.
  
  
  METHODS
  Cell lines of lung adenocarcinoma (A549), breast cancer (MCF7) and hepatocellular carcinoma (HepG2) were co-cultured with T, B and NK cells before and after EMT induction by either the supernatant of mixed-lymphocyte reactions or inflammatory cytokines.
  
  
  RESULTS
  EMT occurrence following inflammatory priming elicited multiple immune-regulatory effects in cancer cells resulting in NK and T-cell apoptosis, inhibition of lymphocyte proliferation and stimulation of regulatory T and B cells. Indoleamine 2,3-dioxygenase, but not Fas ligand pathway, was involved at least in part in these effects, as shown by the use of specific inhibitors.
  
  
  CONCLUSIONS
  EMT induced by inflammatory stimuli confers to cancer cells some mesenchymal stromal cell-like immune-modulatory properties, which could be a cue for cancer progression and metastatic dissemination by favouring immune escape.
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: M
authors: M
authors: Ricciardi
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: M
authors: M
authors: Zanotto
authors: Department of Surgery, University of Verona, Verona 37134, Italy.
authors: G
authors: G
authors: Malpeli
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: G
authors: G
authors: Bassi
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: O
authors: O
authors: Perbellini
authors: Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona 37134, Italy.
authors: M
authors: M
authors: Chilosi
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: F
authors: F
authors: Bifari
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona 37134, Italy.
authors: M
authors: M
authors: Krampera
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D056945:Hep G2 Cells; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase