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Type: Journal article
Title: Inflammatory peroxidases promote breast cancer progression in mice via regulation of the tumour microenvironment
Author: Panagopoulos, V.
Leach, D.
Zinonos, I.
Ponomarev, V.
Licari, G.
Liapis, V.
Ingman, W.
Anderson, P.
DeNichilo, M.
Evdokiou, A.
Citation: International Journal of Oncology, 2017; 50(4):1191-1200
Publisher: Spandidos Publications
Issue Date: 2017
ISSN: 1019-6439
Statement of
Vasilios Panagopoulos, Damien A. Leach, Irene Zinonos, Vladimir Ponomarev, Giovanni Licari, Vasilios Liapis, Wendy V. Ingman Peter Anderson, Mark O. DeNichilo, Andreas Evdokiou
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.
Keywords: Breast
Mice, Inbred BALB C
Breast Neoplasms
Mammary Neoplasms, Experimental
Lung Neoplasms
Disease Progression
Neovascularization, Pathologic
Collagen Type I
Eosinophil Peroxidase
Recombinant Proteins
Collagen Type IV
Cell Movement
Cyclooxygenase 2
Matrix Metalloproteinase 3
Matrix Metalloproteinase 1
Molecular Targeted Therapy
Tumor Microenvironment
Primary Cell Culture
DOI: 10.3892/ijo.2017.3883
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