Background:Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood.Methods:This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts.Results:Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment.Conclusions:These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis.
背景：三阴性乳腺癌（TNBC）较其他乳腺癌类型更易发生肺转移，但转移灶肿瘤微环境（TME）内的分子相互作用机制尚不明确。方法：本探索性研究旨在通过共培养系统模拟肺转移TME，探究MDA-MB-231三阴性乳腺癌细胞与MRC-5肺成纤维细胞之间的代谢相互作用。研究同时使用维生素D或维生素E处理共培养体系，评估这些营养保健品对TNBC细胞与成纤维细胞间代谢交流的影响。结果：研究发现共培养诱导成纤维细胞活化为癌症相关成纤维细胞（CAFs），其α-SMA和FAP表达增加可证实。代谢特征分析显示，共培养中的TNBC细胞与氧化磷酸化（OXPHOS）及谷氨酰胺代谢相关酶的表达升高，而成纤维细胞则呈现与糖酵解及乳酸代谢一致的代谢特征。维生素D抑制了成纤维细胞中的乳酸代谢和HIF-1α表达，同时降低癌细胞中TCA循环活性，提示其可能具有破坏致癌性代谢交互的作用。相反，维生素E处理与乳腺癌细胞中TCA循环及氧化代谢相关标志物表达增加相关，但对成纤维细胞的糖酵解无显著影响。这种差异化的代谢反应可能导致肿瘤微环境内的代谢异质性。结论：本研究为理解肺转移TME中TNBC的代谢动态提供了重要见解，证实维生素D与E对癌细胞与成纤维细胞间的代谢交互具有不同调节作用。这些发现对转移性TNBC患者补充维生素D和E的潜在应用具有重要意义，值得进一步深入分析。
肿瘤(癌症)患者之家