Abstract IA08: Oxidative stress inhibits distant metastasis by human melanoma cells
| Autor: | Elena Piskounova, Sean J. Morrison, Michalis Agathocleous, Ralph J. DeBerardinis |
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| Rok vydání: | 2016 |
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| Zdroj: | Molecular Cancer Research. 14:IA08-IA08 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | Solid cancer cells commonly enter the blood and disseminate systemically but are highly inefficient at forming distant metastases for poorly understood reasons. We studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NSG mice. All melanomas had high frequencies of cells that formed subcutaneous tumors, but much lower percentages of cells that formed tumors after intravenous or intrasplenic transplantation, particularly among inefficient metastasizers. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumors. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence upon NADPH-generating enzymes in the folate pathway. Anti-oxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumors in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo. Citation Format: Elena Piskounova, Michalis Agathocleous, Ralph J. DeBerardinis, Sean J. Morrison. Oxidative stress inhibits distant metastasis by human melanoma cells. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr IA08. |
| Databáze: | OpenAIRE |
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