The role of peroxidasin in solid cancer progression

Abstract

Peroxidasin is a heme-containing peroxidase enzyme that plays a vital role in the cross-linking of collagen IV molecules in basement membranes. Collagen IV cross-links are essential for providing structure and mechanical stability throughout tissue development, homeostasis, and wound healing. During cancer progression, the basement membrane is degraded, and proteins typically found in the basement membrane, including peroxidasin and collagen IV, can be found spread throughout the tumour microenvironment where they interact with cancer cells and alter cell behaviour. Whilst peroxidasin is reported to be up-regulated in a number of different cancers, the role that it plays in disease progression and metastasis has only recently begun to be studied. This review highlights the current literature exploring the known roles of peroxidasin in normal tissues and cancer progression, regulators of peroxidasin expression, and the reported relationships between peroxidasin expression and patient outcome in cancer.

Inflammation-Associated Cytotoxic Agents in Tumorigenesis

“…In invasive metastatic melanoma cells, a high expression of peroxidasin was reported [ 428 ]. Peroxidasin is upregulated in several kinds of cancers [ 429 ]. Abnormal collagen IV cross-linking by peroxidasin leads to an exceedingly dense ECM and a disordered matrix structure, as reported for lung tissue.…”

Peroxidasin Inhibition by Phloroglucinol and Other Peroxidase Inhibitors

“…PXDN was shown to play an adverse role in various cardiovascular conditions including hypertensionassociated endothelial dysfunction [16][17][18], vascular remodelling and calcification [19], cardiac hypertrophy [18], atherosclerosis [20][21][22], aortic aneurysms [23], ischemic cardiac injury and fibrosis [24], as well as pulmonary arterial hypertension [25]. PXDN is upregulated in tissue fibrosis [2,26] and contributes to the progression of numerous types of cancer [27][28][29][30][31][32]. PXDN activity was shown to promote angiogenesis [33] and PXDN expression is associated with an increased invasive potential of cancer cells [29], possibly due to the remodelling of the tumour ECM to promote a permissive environment for cell invasion and metastasis.…”

“…Antioxidants 2024, 13, 23 2 of 20 cardiac injury and fibrosis [24], as well as pulmonary arterial hypertension [25]. PXDN is upregulated in tissue fibrosis [2,26] and contributes to the progression of numerous types of cancer [27][28][29][30][31][32]. PXDN activity was shown to promote angiogenesis [33] and PXDN expression is associated with an increased invasive potential of cancer cells [29], possibly due to the remodelling of the tumour ECM to promote a permissive environment for cell invasion and metastasis.…”