Metastasizing cells undergo metabolic changes, increasing their ability to withstand oxidative stress
TUESDAY, Oct. 27, 2015 (HealthDay News) — Oxidative stress inhibits metastasis by melanoma cells, according to an experimental study published online Oct. 14 in Nature.
Elena Piskounova, Ph.D., from the University of Texas Southwestern Medical Center in Dallas, and colleagues analyzed human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg−/− (NSG) mice.
The researchers found that the melanomas had high frequencies of cells that formed subcutaneous tumors, but lower percentages of cells that formed tumors following intravenous or intrasplenic transplantation; this was especially true for melanomas that metastasized inefficiently. Oxidative stress was seen in melanoma cells in the blood and visceral organs, but not in established subcutaneous tumor. During metastasis, successfully metastasizing melanomas underwent reversible metabolic changes, which increased their capacity to withstand oxidative stress, including elevated dependence on NADPH-generating enzymes within the folate pathway. Distant metastasis was promoted by antioxidants in NSG mice. Inhibition of folate pathway correlated with inhibition of distant metastasis with no significant effect on the growth of subcutaneous tumors in the same mice.
“Our results suggest that antioxidants promote disease progression, at least in melanoma, by promoting metastasis,” the authors write.
Several authors disclosed financial ties to pharmaceutical companies, several of which provided study medication, equipment, or supplies.
Abstract
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