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

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 24h 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) andmonocytes (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-alpha-Tumor Necrosis Factor-alpha) were higher in both groups of implant-bearing tumors and in serumfromthose 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.