{"title":"1α,25-二羟维生素 D 下调脂肪细胞对乳腺癌细胞迁移和脂肪因子释放的影响","authors":"Chaehyun Yum, Chaylen Andolino, Brienna Larrick, Madeline P Sheeley, Dorothy Teegarden","doi":"10.3390/nu16183153","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>Excess adiposity is associated with a higher risk of breast cancer metastasis and mortality. Evidence suggests that dietary vitamin D inhibits breast cancer metastasis. However, the mechanistic link between vitamin D's regulation of adipocyte metabolism and metastasis has not been previously investigated. Therefore, the purpose of these experiments was to examine the effect of the active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)<sub>2</sub>D), on adipocyte release of bioactive compounds and whether the impact on adipocytes leads to inhibition of breast cancer cell migration, an important step of metastasis.</p><p><strong>Methods: </strong>Differentiated 3T3-L1 adipocytes were treated with 1,25(OH)<sub>2</sub>D for two days, followed by either harvesting the adipocytes or collecting adipocyte-conditioned media without 1,25(OH)<sub>2</sub>D. A transwell migration assay was conducted with vehicle- or 1,25(OH)<sub>2</sub>D-conditioned media. In order to explore the mechanism underlying effects on breast cancer metastatic capability, the mRNA expression of leptin, adiponectin, insulin-like growth factor (IGF-1), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) was measured in adipocytes following either vehicle or 1,25(OH)<sub>2</sub>D treatment.</p><p><strong>Results: </strong>Conditioned media from 1,25(OH)<sub>2</sub>D-treated adipocytes inhibited the migration of metastatic MDA-MB-231 breast cancer cells compared to conditioned media from vehicle-treated adipocytes. Treatment of adipocytes with 1,25(OH)<sub>2</sub>D decreased mRNA expression of leptin, adiponectin, IGF-1, IL-6, and MCP-1. Consistent with mRNA expression, concentrations of leptin, adiponectin, IGF-1, and IL-6 in adipocyte-conditioned media were decreased with 1,25(OH)<sub>2</sub>D treatment, although MCP-1 remained unchanged.</p><p><strong>Conclusions: </strong>In summary, these results suggest that 1,25(OH)<sub>2</sub>D alters adipocyte secretions to prevent breast cancer metastasis.</p>","PeriodicalId":19486,"journal":{"name":"Nutrients","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434957/pdf/","citationCount":"0","resultStr":"{\"title\":\"1α,25-Dihydroxyvitamin D Downregulates Adipocyte Impact on Breast Cancer Cell Migration and Adipokine Release.\",\"authors\":\"Chaehyun Yum, Chaylen Andolino, Brienna Larrick, Madeline P Sheeley, Dorothy Teegarden\",\"doi\":\"10.3390/nu16183153\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/objectives: </strong>Excess adiposity is associated with a higher risk of breast cancer metastasis and mortality. Evidence suggests that dietary vitamin D inhibits breast cancer metastasis. However, the mechanistic link between vitamin D's regulation of adipocyte metabolism and metastasis has not been previously investigated. Therefore, the purpose of these experiments was to examine the effect of the active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)<sub>2</sub>D), on adipocyte release of bioactive compounds and whether the impact on adipocytes leads to inhibition of breast cancer cell migration, an important step of metastasis.</p><p><strong>Methods: </strong>Differentiated 3T3-L1 adipocytes were treated with 1,25(OH)<sub>2</sub>D for two days, followed by either harvesting the adipocytes or collecting adipocyte-conditioned media without 1,25(OH)<sub>2</sub>D. A transwell migration assay was conducted with vehicle- or 1,25(OH)<sub>2</sub>D-conditioned media. In order to explore the mechanism underlying effects on breast cancer metastatic capability, the mRNA expression of leptin, adiponectin, insulin-like growth factor (IGF-1), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) was measured in adipocytes following either vehicle or 1,25(OH)<sub>2</sub>D treatment.</p><p><strong>Results: </strong>Conditioned media from 1,25(OH)<sub>2</sub>D-treated adipocytes inhibited the migration of metastatic MDA-MB-231 breast cancer cells compared to conditioned media from vehicle-treated adipocytes. Treatment of adipocytes with 1,25(OH)<sub>2</sub>D decreased mRNA expression of leptin, adiponectin, IGF-1, IL-6, and MCP-1. Consistent with mRNA expression, concentrations of leptin, adiponectin, IGF-1, and IL-6 in adipocyte-conditioned media were decreased with 1,25(OH)<sub>2</sub>D treatment, although MCP-1 remained unchanged.</p><p><strong>Conclusions: </strong>In summary, these results suggest that 1,25(OH)<sub>2</sub>D alters adipocyte secretions to prevent breast cancer metastasis.</p>\",\"PeriodicalId\":19486,\"journal\":{\"name\":\"Nutrients\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11434957/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nutrients\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/nu16183153\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrients","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/nu16183153","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
摘要
背景/目的:过度肥胖与较高的乳腺癌转移风险和死亡率有关。有证据表明,膳食中的维生素 D 可抑制乳腺癌的转移。然而,维生素 D 对脂肪细胞代谢的调节与转移之间的机理联系此前尚未得到研究。因此,这些实验的目的是研究维生素 D 的活性形式--1α,25-二羟维生素 D(1,25(OH)2D)对脂肪细胞释放生物活性化合物的影响,以及对脂肪细胞的影响是否会导致抑制乳腺癌细胞迁移(转移的重要步骤):方法:用1,25(OH)2D处理分化的3T3-L1脂肪细胞两天,然后收获脂肪细胞或收集不含1,25(OH)2D的脂肪细胞调节培养基。使用含 1,25(OH)2D的培养基或 1,25(OH)2D调节培养基进行跨孔迁移试验。为了探究影响乳腺癌转移能力的机制,研究人员测量了经车辆或 1,25(OH)2D 处理的脂肪细胞中瘦素、脂肪连素、胰岛素样生长因子(IGF-1)、白细胞介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的 mRNA 表达:结果:1,25(OH)2D处理过的脂肪细胞的条件培养基与1,25(OH)2D处理过的脂肪细胞的条件培养基相比,能抑制转移性MDA-MB-231乳腺癌细胞的迁移。用1,25(OH)2D处理脂肪细胞可降低瘦素、脂肪连素、IGF-1、IL-6和MCP-1的mRNA表达。与 mRNA 表达一致的是,1,25(OH)2D 处理后,脂肪细胞调节培养基中瘦素、脂肪连通素、IGF-1 和 IL-6 的浓度降低,但 MCP-1 保持不变:总之,这些结果表明,1,25(OH)2D 可改变脂肪细胞的分泌,从而防止乳腺癌转移。
1α,25-Dihydroxyvitamin D Downregulates Adipocyte Impact on Breast Cancer Cell Migration and Adipokine Release.
Background/objectives: Excess adiposity is associated with a higher risk of breast cancer metastasis and mortality. Evidence suggests that dietary vitamin D inhibits breast cancer metastasis. However, the mechanistic link between vitamin D's regulation of adipocyte metabolism and metastasis has not been previously investigated. Therefore, the purpose of these experiments was to examine the effect of the active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)2D), on adipocyte release of bioactive compounds and whether the impact on adipocytes leads to inhibition of breast cancer cell migration, an important step of metastasis.
Methods: Differentiated 3T3-L1 adipocytes were treated with 1,25(OH)2D for two days, followed by either harvesting the adipocytes or collecting adipocyte-conditioned media without 1,25(OH)2D. A transwell migration assay was conducted with vehicle- or 1,25(OH)2D-conditioned media. In order to explore the mechanism underlying effects on breast cancer metastatic capability, the mRNA expression of leptin, adiponectin, insulin-like growth factor (IGF-1), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) was measured in adipocytes following either vehicle or 1,25(OH)2D treatment.
Results: Conditioned media from 1,25(OH)2D-treated adipocytes inhibited the migration of metastatic MDA-MB-231 breast cancer cells compared to conditioned media from vehicle-treated adipocytes. Treatment of adipocytes with 1,25(OH)2D decreased mRNA expression of leptin, adiponectin, IGF-1, IL-6, and MCP-1. Consistent with mRNA expression, concentrations of leptin, adiponectin, IGF-1, and IL-6 in adipocyte-conditioned media were decreased with 1,25(OH)2D treatment, although MCP-1 remained unchanged.
Conclusions: In summary, these results suggest that 1,25(OH)2D alters adipocyte secretions to prevent breast cancer metastasis.
期刊介绍:
Nutrients (ISSN 2072-6643) is an international, peer-reviewed open access advanced forum for studies related to Human Nutrition. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.