Oxidativestressinbibitsdistantmetastasisbyhumanmelanomacells分析.pptxVIP

University of Texas Southwestern Medical Center University of Michigan;Background;Materials and methods;Content;Blood and viscera are hostile to metastasis;A;;;Q1.Whether the main difference between efficiently and inefficiently metastasizing melanomas is the ability to enter the circulation?;;Therefore, the ability to enter circulation is not the only factor that limits distant metastasis. The blood was more hostile to melanoma cells than the subcutaneous environment. ;Q2.Whether distant metastasis is limited mainly by survival in the blood?;;The ability to survive in the circulation is therefore not the only factor that limits distant metastasis. The spleen is also a relatively hostile environment for melanoma cells.;1.Blood and viscera are hostile to metastasis;Reversible tropic changes during metastasis;Q1.Whether melanoma cells undergo changes in properties during metastasis?;This suggests melanoma cells adapt to the sites of metastasis as they metastasize.;Q2.Whether the changes were irreversible (for example, genetic) or reversible (for example, epigenetic or metabolic)?;The changes in tumorigenic tropism during metastasis are thus reversible. Since these reversible changes were observed very consistently, even in small numbers of melanoma cells, these changes cannot reflect selection for rare genetic events during metastasis followed by reversion mutations after subcutaneous re-transplantation.;2.Reversible tropic changes during metastasis;Oxidative stress limits distant metastasis;Q1.Whether successfully metastasizing cells undergo reversible metabolic changes that increase their capacity to withstand oxidative stress?;a.unsupervised clustering of metabolomics;reversible metabolic changes;Melanoma cells undergo reversible changes in tropism during metastasis;b.GSH/GSSG;c.ROS level;d.Mitochondrial mass and membrane potential;e.Changes are reversible;Q2.Whether oxidative stress limits melanoma metastasis?;Method:we subcutaneously transplanted efficiently