Differential Contribution of Acute and Chronic Inflammation to the Development of Murine Mammary 4T1 Tumors

• Published in: PloS one Vol. 10; no. 7; p. e0130809
• Main Authors: Rodrigues Viana, Celso Tarso, Castro, Pollyana Ribeiro, Marques, Suzane Motta, Paz Lopes, Miriam Teresa, Gonçalves, Ricardo, Campos, Paula Peixoto, Andrade, Silvia Passos
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.07.2015; Public Library of Science (PLoS)
• Subjects: Acetylglucosaminidase - immunology; Acetylglucosaminidase - metabolism; Acute Disease; Analysis; Angiogenesis; Animals; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Biophysics; Breast cancer; Cancer; Chemokines; Chronic Disease; Cytokines; Dendritic cells; Development and progression; Disease Progression; Enzymes; Flow Cytometry; Growth factors; Implantation; Implants; Inflammation; Inflammation - immunology; Inflammation - metabolism; Leukocytes; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Macrophages; Macrophages - immunology; Macrophages - metabolism; Male; Mammary gland; Mammary Neoplasms, Experimental - blood supply; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - metabolism; Markers; Metastasis; Mice, Inbred BALB C; Monocytes; Monocytes - immunology; Monocytes - metabolism; N-Acetylglucosaminidase; Neovascularization, Pathologic - immunology; Neovascularization, Pathologic - metabolism; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Pathology; Peroxidase - immunology; Peroxidase - metabolism; Physiology; Polyurethane; Polyurethane resins; Polyurethanes; Rodents; Time Factors; Transplants & implants; Tumor Burden - immunology; Tumor cells; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Tumorigenesis; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - immunology; Vascular Endothelial Growth Factor A - metabolism
• DOI: 10.1371/journal.pone.0130809
• ISSN: 1932-6203

Based on the notion that inflammation favors tumorigenesis, our experiments comparatively assessed the influence of acute and chronic inflammation on the development of a murine mammary tumor (4T1). In addition, we characterized angiogenic and inflammatory markers in the tumor tissue and systemically. Subcutaneous implantation of polyether-polyurethane sponge discs in Balb/c mice was used to host 4T1 tumor cells (1x10(6)), which were inoculated intraimplant 24 h or 10 days post implantation. Flow cytometric analysis of enzyme-digested implants revealed that, after 24 hours, the population of leukocytes was primarily characterized by neutrophils (42.53% +/- 8.45) and monocytes (37.53% +/- 7.48), with some lymphocytes (16.27% +/- 4.0) and a few dendritic cells (1.82% +/- 0.36). At 10 days, macrophages were predominant (37.10% +/- 4.54), followed by lymphocytes (28.1% +/- 4.77), and monocytes (22.33% +/- 3.05), with some dendritic cells (13.60% +/- 0.55) and neutrophils (11.07% +/- 2.27). A mammary tumor grown in a chronic inflammatory environment was 2-fold when compared with one grown in acute inflammation and 5-fold when compared with tumor alone. The levels of pro-angiogenic cytokine (VEGF-Vascular Endothelial Growth Factor) were higher in implant-bearing tumor when 4T1 cells were grown in 10-day old implants as compared to the VEGF levels of the two other groups. Overall, the levels of the inflammatory markers evaluated (NAG -N-acetylglucosaminidase, TNF-α-Tumor Necrosis Factor-α) were higher in both groups of implant-bearing tumors and in serum from those animals when compared with the tumor alone levels. This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.