title: A by-product of glutathione production in cancer cells may cause disruption in bone metabolic processes.
abstract: Bone is a frequent site for metastasis of breast and prostate cancers, often resulting in pathologic changes in bone metabolism and severe pain. The mechanisms involved are not well understood, but tumour cells may release factors that interfere with bone homeostasis. Several observations have led us to hypothesize that the functional disruptions in bone metastasis are the result of a biological process common to many cell types. The high metabolic activity characteristic of cancer cells often upregulates oxidative stress protection mechanisms such as the antioxidant molecule glutathione. In maintaining redox balance, this normal metabolic response may result in unintended pathologic effects in certain sensitive organ sites. Malignant glioma cells kill surrounding neurons in the brain specifically by secreting the amino acid glutamate, an obligatory waste product of glutathione synthesis. We suggest that glutamate release is a plausible mechanism that may account for the pathologic changes in bone metastasis, since bone, like brain, is also highly sensitive to glutamatergic disruption. This report reviews the available evidence to draw a mechanistic connection between tumour cell oxidative stress and the pathology seen in patients with bone metastasis.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, 699 Concession Street, Hamilton, ON L8V 5C2, Canada.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Seidlitz
authors.forename: Mohit K
authors.initials: MK
authors.lastname: Sharma
authors.forename: Gurmit
authors.initials: G
authors.lastname: Singh
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D005978:Glutathione / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D005978:Glutathione