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

Rodrigues Viana CT, Castro PR, Marques SM, Paz Lopes MT, Gonçalves R, Campos PP, Andrade SP - PLoS ONE (2015)

Bottom Line: 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).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.This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

Sponge implant model and diagrammatic timeline of the experiments.Implantation of polyether polyurethane sponges in the subcutaneous space in the back of Balb/c mice (A and B). Diagram representing the time line of sponge implantation for inflammatory biomarkers and cytometry analysis (C).
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pone.0130809.g001: Sponge implant model and diagrammatic timeline of the experiments.Implantation of polyether polyurethane sponges in the subcutaneous space in the back of Balb/c mice (A and B). Diagram representing the time line of sponge implantation for inflammatory biomarkers and cytometry analysis (C).

Mentions: Polyether-polyurethane sponge (Vitafoam Ltd. Manchester, UK) was used as the implanted material to provide the inflammatory environment to host the tumor cells. The sponge discs, 5mm thick×8mm diameter, were soaked overnight in 70% v/v ethanol and sterilized by boiling in distilled water for 15min before implantation. The animals were then anesthetized, the right side of their back shaved, and the exposed skin wiped with 70% ethanol. One sponge disc per animal was aseptically implanted into a subcutaneous pouch, which had been made with curved artery forceps through a 1 cm long dorsal mid-line incision 4 cm away from the implant location (Fig 1A and 1B). Placement of sponge discs in this manner reduces the confounding influence of the wound incision over the implant. The incisions were closed with a silk braided non-absorbable suture. In this series of experiments, the implants of twenty-four mice were removed at day 1 or at day 10 post-implantation to analyze the inflammatory markers of both acute and chronic inflammatory processes (myeloperoxidase-MPO, n-acetyl-β-D-glucosaminidase- NAG, VEGF and TNF-α) and for cell content determination by flow cytometry. The schematic diagram (Fig 1C) shows the timeline of sponge implantation and removal.


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

Rodrigues Viana CT, Castro PR, Marques SM, Paz Lopes MT, Gonçalves R, Campos PP, Andrade SP - PLoS ONE (2015)

Sponge implant model and diagrammatic timeline of the experiments.Implantation of polyether polyurethane sponges in the subcutaneous space in the back of Balb/c mice (A and B). Diagram representing the time line of sponge implantation for inflammatory biomarkers and cytometry analysis (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4497676&req=5

pone.0130809.g001: Sponge implant model and diagrammatic timeline of the experiments.Implantation of polyether polyurethane sponges in the subcutaneous space in the back of Balb/c mice (A and B). Diagram representing the time line of sponge implantation for inflammatory biomarkers and cytometry analysis (C).
Mentions: Polyether-polyurethane sponge (Vitafoam Ltd. Manchester, UK) was used as the implanted material to provide the inflammatory environment to host the tumor cells. The sponge discs, 5mm thick×8mm diameter, were soaked overnight in 70% v/v ethanol and sterilized by boiling in distilled water for 15min before implantation. The animals were then anesthetized, the right side of their back shaved, and the exposed skin wiped with 70% ethanol. One sponge disc per animal was aseptically implanted into a subcutaneous pouch, which had been made with curved artery forceps through a 1 cm long dorsal mid-line incision 4 cm away from the implant location (Fig 1A and 1B). Placement of sponge discs in this manner reduces the confounding influence of the wound incision over the implant. The incisions were closed with a silk braided non-absorbable suture. In this series of experiments, the implants of twenty-four mice were removed at day 1 or at day 10 post-implantation to analyze the inflammatory markers of both acute and chronic inflammatory processes (myeloperoxidase-MPO, n-acetyl-β-D-glucosaminidase- NAG, VEGF and TNF-α) and for cell content determination by flow cytometry. The schematic diagram (Fig 1C) shows the timeline of sponge implantation and removal.

Bottom Line: 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).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.This inflammation-related difference in tumor growth may provide new insights into the contribution of different inflammatory cell populations to cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus