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

PLoS One. 2015 Jul 9;10(7):e0130809. doi: 10.1371/journal.pone.0130809. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / immunology
  • Acetylglucosaminidase / metabolism
  • Acute Disease
  • Animals
  • Biomarkers, Tumor / immunology*
  • Biomarkers, Tumor / metabolism
  • Chronic Disease
  • Disease Progression
  • Flow Cytometry
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice, Inbred BALB C
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / metabolism
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Peroxidase / immunology
  • Peroxidase / metabolism
  • Time Factors
  • Tumor Burden / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Peroxidase
  • Acetylglucosaminidase

Grants and funding

The author Celso Tarso received funding as a (PhD scholarship) from CAPES-Brazil for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.