{"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}
引用次数: 0
Abstract
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
