Interdepartmental Nutrition Program, Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
Nutrients. 2024 Sep 18;16(18):3153. doi: 10.3390/nu16183153.
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)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.
Differentiated 3T3-L1 adipocytes were treated with 1,25(OH)D for two days, followed by either harvesting the adipocytes or collecting adipocyte-conditioned media without 1,25(OH)D. A transwell migration assay was conducted with vehicle- or 1,25(OH)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)D treatment.
Conditioned media from 1,25(OH)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)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)D treatment, although MCP-1 remained unchanged.
In summary, these results suggest that 1,25(OH)D alters adipocyte secretions to prevent breast cancer metastasis.
背景/目的：过多的体脂与乳腺癌转移和死亡率升高有关。有证据表明，膳食维生素 D 可抑制乳腺癌转移。然而，维生素 D 调节脂肪细胞代谢与转移之间的机制联系尚未得到研究。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）D）对脂肪细胞释放生物活性化合物的影响，以及这种对脂肪细胞的影响是否会导致乳腺癌细胞迁移的抑制，这是转移的重要步骤。
用 1,25（OH）D 处理分化的 3T3-L1 脂肪细胞两天，然后收获脂肪细胞或不含有 1,25（OH）D 的脂肪细胞条件培养基。用载体或 1,25（OH）D 条件培养基进行 Transwell 迁移测定。为了探讨对乳腺癌转移能力的影响的机制，在脂肪细胞中用载体或 1,25（OH）D 处理后测量瘦素、脂联素、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。
与载体处理的脂肪细胞条件培养基相比，1,25（OH）D 处理的脂肪细胞的条件培养基抑制了转移性 MDA-MB-231 乳腺癌细胞的迁移。用 1,25（OH）D 处理脂肪细胞会降低瘦素、脂联素、IGF-1、IL-6 和 MCP-1 的 mRNA 表达。与 mRNA 表达一致，尽管 MCP-1 保持不变，但脂肪细胞条件培养基中的瘦素、脂联素、IGF-1 和 IL-6 浓度随着 1,25（OH）D 处理而降低。
总之，这些结果表明 1,25（OH）D 改变脂肪细胞的分泌以防止乳腺癌转移。
