Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment

  • Authors:
    • Vasilios Panagopoulos
    • Damien A. Leach
    • Irene Zinonos
    • Vladimir Ponomarev
    • Giovanni Licari
    • Vasilios Liapis
    • Wendy V. Ingman
    • Peter Anderson
    • Mark O. DeNichilo
    • Andreas Evdokiou
  • View Affiliations

  • Published online on: February 20, 2017     https://doi.org/10.3892/ijo.2017.3883
  • Pages: 1191-1200
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Abstract

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, well known for their antimicrobial activity, are released in high quantities by infiltrating immune cells in breast cancer. However, the functional importance of their presence within the tumour microenvironment is unclear. We have recently described a new role for peroxidases as key regulators of fibroblast and endothelial cell functionality. In the present study, we investigate for the first time, the ability of peroxidases to promote breast cancer development and progression. Using the 4T1 syngeneic murine orthotopic breast cancer model, we examined whether increased levels of peroxidases in developing mammary tumours influences primary tumour growth and metastasis. We showed that MPO and EPO stimulation increased mammary tumour growth and enhanced lung metastases, effects that were associated with reduced tumour necrosis, increased collagen deposition and neo-vascularisation within the primary tumour. In vitro, peroxidase treatment, robustly stimulated human mammary fibroblast migration and collagen type I and type VI secretion. Mechanistically, peroxidases induced the transcription of pro-tumorigenic and metastatic MMP1, MMP3 and COX-2 genes. Taken together, these findings identify peroxidases as key contributors to cancer progression by augmenting pro-tumorigenic collagen production and angiogenesis. Importantly, this identifies inflammatory peroxidases as therapeutic targets in breast cancer therapy.
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April-2017
Volume 50 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Panagopoulos V, Leach DA, Zinonos I, Ponomarev V, Licari G, Liapis V, Ingman WV, Anderson P, DeNichilo MO, Evdokiou A, Evdokiou A, et al: Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment. Int J Oncol 50: 1191-1200, 2017
APA
Panagopoulos, V., Leach, D.A., Zinonos, I., Ponomarev, V., Licari, G., Liapis, V. ... Evdokiou, A. (2017). Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment. International Journal of Oncology, 50, 1191-1200. https://doi.org/10.3892/ijo.2017.3883
MLA
Panagopoulos, V., Leach, D. A., Zinonos, I., Ponomarev, V., Licari, G., Liapis, V., Ingman, W. V., Anderson, P., DeNichilo, M. O., Evdokiou, A."Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment". International Journal of Oncology 50.4 (2017): 1191-1200.
Chicago
Panagopoulos, V., Leach, D. A., Zinonos, I., Ponomarev, V., Licari, G., Liapis, V., Ingman, W. V., Anderson, P., DeNichilo, M. O., Evdokiou, A."Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment". International Journal of Oncology 50, no. 4 (2017): 1191-1200. https://doi.org/10.3892/ijo.2017.3883