title: Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment.
abstract: BACKGROUND
  Malignant peritoneal mesothelioma (MPM) is a rare cancer arising from mesothelial cells lining the peritoneal surface. Little is known about the tumor microenvironment in regulating MPM oncogenesis. The current study defined the chemokine/cytokine expression profile and inflammatory responses within the MPM microenvironment.
  
  
  METHODS
  Levels of 10 cytokines (Fractalkine, IFNγ, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, VEGF) in matched ascites and sera from 15 MPM patients were measured using Milliplex immunoassays. Sera from six normal control sera were included. Statistical analyses included the Wilcoxon signed-rank test, the Mann-Whitney U test, bivariate analysis, and the R (2) coefficient of correlation.
  
  
  RESULTS
  The median levels of IL-6 (3190 vs 3.18 ng/ml; p < 0.001), IL-8 (118 vs 4.93 ng/ml; p < 0.001), IP-10 (3923 vs 384 ng/ml; p < 0.001), and MCP-1 (2886 vs 544 ng/ml; p = 0.005) were significantly higher in the MPM ascites than in the matched MPM serum. In the MPM serum samples, the levels of IL-8 (4.93 vs 1.52 ng/ml; p = 0.002), MIP-1β (53.8 vs 22.3; p = 0.016), TNFα (9.97 vs 4.5 ng/ml; p = 0.013), and VEGF (277 vs 105.4 ng/ml; p = 0.036) were significantly higher than in the control sera.
  
  
  CONCLUSIONS
  The chemokines/cytokines in the MPM tumor microenvironment are distinct from those associated with inflammatory responses to infection or injury (e.g., IL-1, IL-2, TNFα, IFNγ). These local changes reflect active reciprocal communication between tumor and associated stroma, which the authors predict is integral to MPM oncogenesis. Future studies will test this hypothesis and identify potential serum biomarkers for MPM.
authors.affiliation: Department of Surgery, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Judge
authors.affiliation: Department of Surgery, Creighton University Medical Center, Omaha, NE, USA. peterthomas@creighton.edu.|Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA. peterthomas@creighton.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Govindarajan
authors.affiliation: Department of Pathology, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Surgery, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Loggie
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008654:Mesothelioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000086002:Mesothelioma, Malignant; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D015996:Survival Rate; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; D016207:Cytokines