Free Radicals, pro and con

[Rollo]

17. FREE RADICAL PATHOPHYSIOLOGY

FREE RADICAL PATHOPHYSIOLOGY

Oxidative modification of collagen influences breast cancer stem cell response to HNE

Breast cancer represents leading cause of mortality and morbidity in women, mostly due to property of primary tumor to metastasize. It was revealed recently that metastases comprise a fraction of stem-like cells, denoted as cancer stem cells (CSCs), usually located in the bone marrow. CSCs are of great importance in cancer biology as they are involved in blood vessel formation, promotion of cell motility and resistance to therapies and especially to metastasis development. One of the important factors influencing the stem cell destiny is their microenvironment and their interaction with extracellular matrix (ECM). Taking together the role of ECM in determining cell destiny and the involvement of lipids, lipid metabolism and lipid peroxidation in breast cancer development, we wanted to investigate the interactions between ECM and the growth regulating lipid peroxidation product 4-hydroxynonenal (HNE) on breast cancer stem cells. Our results indicate that oxidative modification of ECM collagen influences CSC growth, morphology and reaction to extracellular oxidative stress mediated by HNE and the growth inhibiting effects of this aldehyde. This is of importance as oxidative modification of ECM proteins could occur during local inflammation and during chemotherapies which cause lipid peroxidation. These modifications could be toxic for cancer and change gene expression, motility or stage