Shiho Hashiguchi, Tomoko Tanaka, Ryosuke Mano, Seiji Kondo, Shohta Kodama
{"title":"SLC7A11/xCT 介导的胱氨酸摄取调节细胞内谷胱甘肽并促进淋巴管内皮细胞的抗氧化防御。","authors":"Shiho Hashiguchi, Tomoko Tanaka, Ryosuke Mano, Seiji Kondo, Shohta Kodama","doi":"10.21873/anticanres.17393","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>In a tongue-submandibular lymph node (SLN) metastasis model, the cystine/glutamate transporter solute carrier family 7, member 11 (Slc7a11), also known as xCT, was found to increase in lymphatic endothelial cells (LECs) within SLNs prior to melanoma cell metastasis. However, the precise mechanism by which xCT influences LECs remains unclear. This study aimed to explore the role of xCT in primary cultured LECs.</p><p><strong>Materials and methods: </strong>To determine whether xCT is involved in cystine uptake and glutathione (GSH) synthesis in primary cultured LECs, cystine uptake and GSH assays were conducted. The antioxidant role of xCT was evaluated by measuring intracellular reactive oxygen species (ROS). Additionally, xCT expression was analyzed in human melanoma metastatic lymph nodes using immunohistochemical staining.</p><p><strong>Results: </strong>Slc7a11-knockdown LECs exhibited significantly reduced cystine uptake and intracellular GSH levels. ROS levels in Slc7a11-knockdown LECs were found to be increased compared to those in control LECs under H<sub>2</sub>O<sub>2</sub>-induced oxidative stress conditions. xCT stability is regulated by CD44v; therefore, we evaluated whether LYVE-1, a hyaluronic acid receptor in LECs, regulates xCT expression. LYVE-1 upregulates Slc7a11 mRNA expression, increasing GSH production in LECs. Furthermore, xCT expression was observed in LECs within human melanoma metastatic lymph nodes.</p><p><strong>Conclusion: </strong>xCT functions as a cystine transporter, contributing to increased GSH levels in lymphatic fluid in melanoma metastasis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 1","pages":"65-71"},"PeriodicalIF":1.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SLC7A11/xCT-mediated Cystine Uptake Regulates Intracellular Glutathione and Promotes Antioxidant Defense in Lymphatic Endothelial Cells.\",\"authors\":\"Shiho Hashiguchi, Tomoko Tanaka, Ryosuke Mano, Seiji Kondo, Shohta Kodama\",\"doi\":\"10.21873/anticanres.17393\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>In a tongue-submandibular lymph node (SLN) metastasis model, the cystine/glutamate transporter solute carrier family 7, member 11 (Slc7a11), also known as xCT, was found to increase in lymphatic endothelial cells (LECs) within SLNs prior to melanoma cell metastasis. However, the precise mechanism by which xCT influences LECs remains unclear. This study aimed to explore the role of xCT in primary cultured LECs.</p><p><strong>Materials and methods: </strong>To determine whether xCT is involved in cystine uptake and glutathione (GSH) synthesis in primary cultured LECs, cystine uptake and GSH assays were conducted. The antioxidant role of xCT was evaluated by measuring intracellular reactive oxygen species (ROS). Additionally, xCT expression was analyzed in human melanoma metastatic lymph nodes using immunohistochemical staining.</p><p><strong>Results: </strong>Slc7a11-knockdown LECs exhibited significantly reduced cystine uptake and intracellular GSH levels. ROS levels in Slc7a11-knockdown LECs were found to be increased compared to those in control LECs under H<sub>2</sub>O<sub>2</sub>-induced oxidative stress conditions. xCT stability is regulated by CD44v; therefore, we evaluated whether LYVE-1, a hyaluronic acid receptor in LECs, regulates xCT expression. LYVE-1 upregulates Slc7a11 mRNA expression, increasing GSH production in LECs. Furthermore, xCT expression was observed in LECs within human melanoma metastatic lymph nodes.</p><p><strong>Conclusion: </strong>xCT functions as a cystine transporter, contributing to increased GSH levels in lymphatic fluid in melanoma metastasis.</p>\",\"PeriodicalId\":8072,\"journal\":{\"name\":\"Anticancer research\",\"volume\":\"45 1\",\"pages\":\"65-71\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anticancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21873/anticanres.17393\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17393","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
SLC7A11/xCT-mediated Cystine Uptake Regulates Intracellular Glutathione and Promotes Antioxidant Defense in Lymphatic Endothelial Cells.
Background/aim: In a tongue-submandibular lymph node (SLN) metastasis model, the cystine/glutamate transporter solute carrier family 7, member 11 (Slc7a11), also known as xCT, was found to increase in lymphatic endothelial cells (LECs) within SLNs prior to melanoma cell metastasis. However, the precise mechanism by which xCT influences LECs remains unclear. This study aimed to explore the role of xCT in primary cultured LECs.
Materials and methods: To determine whether xCT is involved in cystine uptake and glutathione (GSH) synthesis in primary cultured LECs, cystine uptake and GSH assays were conducted. The antioxidant role of xCT was evaluated by measuring intracellular reactive oxygen species (ROS). Additionally, xCT expression was analyzed in human melanoma metastatic lymph nodes using immunohistochemical staining.
Results: Slc7a11-knockdown LECs exhibited significantly reduced cystine uptake and intracellular GSH levels. ROS levels in Slc7a11-knockdown LECs were found to be increased compared to those in control LECs under H2O2-induced oxidative stress conditions. xCT stability is regulated by CD44v; therefore, we evaluated whether LYVE-1, a hyaluronic acid receptor in LECs, regulates xCT expression. LYVE-1 upregulates Slc7a11 mRNA expression, increasing GSH production in LECs. Furthermore, xCT expression was observed in LECs within human melanoma metastatic lymph nodes.
Conclusion: xCT functions as a cystine transporter, contributing to increased GSH levels in lymphatic fluid in melanoma metastasis.
期刊介绍：
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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