Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/105718
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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
1791-2423
Statement of
Responsibility: 
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; Fibroblasts; Animals; Mice, Inbred BALB C; Humans; Mice; Breast Neoplasms; Mammary Neoplasms, Experimental; Lung Neoplasms; Disease Progression; Neovascularization, Pathologic; Collagen Type I; Eosinophil Peroxidase; Peroxidase; Recombinant Proteins; Collagen Type IV; Cell Movement; Female; Cyclooxygenase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 1; Molecular Targeted Therapy; Tumor Microenvironment; Primary Cell Culture
Rights: Rightsholder: SPANDIDOS PUBLICATIONS UK LTD.
RMID: 0030065648
DOI: 10.3892/ijo.2017.3883
Grant ID: http://purl.org/au-research/grants/nhmrc/627015
http://purl.org/au-research/grants/nhmrc/1050694
Appears in Collections:Medicine publications

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