Sean Judge1, Peter Thomas2,3, Venkatesh Govindarajan4, Poonam Sharma5, Brian Loggie1. 1. Department of Surgery, Creighton University Medical Center, Omaha, NE, USA. 2. Department of Surgery, Creighton University Medical Center, Omaha, NE, USA. peterthomas@creighton.edu. 3. Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA. peterthomas@creighton.edu. 4. Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE, USA. 5. Department of Pathology, Creighton University Medical Center, Omaha, NE, USA.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Justyna Mikuła-Pietrasik; Paweł Uruski; Kinga Matuszkiewicz; Sebastian Szubert; Rafał Moszyński; Dariusz Szpurek; Stefan Sajdak; Andrzej Tykarski; Krzysztof Książek Journal: Cell Oncol (Dordr) Date: 2016-07-21 Impact factor: 6.730
Authors: Gauri R Varadhachary; Daniel M Halperin; Kanwal Raghav; Suyu Liu; Michael J Overman; Anneleis F Willett; Mark Knafl; Szu-Chin Fu; Anais Malpica; Seema Prasad; Richard E Royal; Christopher P Scally; Paul F Mansfield; Ignacio I Wistuba; Andrew P Futreal; Dipen M Maru; Luisa M Solis Soto; Edwin R Parra Cuentas; Honglei Chen; Pamela Villalobos; Anuj Verma; Armeen Mahvash; Patrick Hwu; Patricia Cortazar; Edward McKenna; Cindy Yun; Shannon Dervin; Katja Schulze; Walter C Darbonne; Ajaykumar C Morani; Scott Kopetz; Keith F Fournier; Scott E Woodman; James C Yao Journal: Cancer Discov Date: 2021-07-14 Impact factor: 39.397