癌细胞的一个既定特征是代谢重编程，主要包括葡萄糖摄取的加剧。肿瘤微环境中的脂肪细胞有助于乳腺癌（BC）的进展，并且对代谢波动高度敏感。以肥胖和/或糖尿病为特征的代谢状况与 BC 发病率和死亡率增加相关。为了探索 BC-脂肪细胞相互作用并确定葡萄糖在这种对话中的影响，将乳腺脂肪源性间充质干细胞 (MAd-MSC) 分化为脂肪细胞，并与 ER BC 细胞共培养，同时暴露于类似于高血糖或正常血糖的葡萄糖浓度。人类（25mM 或 5.5mM）。通过 RNA-Seq 对共培养和单一培养中两种细胞类型的转录组进行分析，以确定脂肪细胞对 BC 细胞的影响，反之亦然 (i)、葡萄糖对 BC 细胞、脂肪细胞 (ii) 及其作用串扰(iii)。值得注意的是，我们提供的证据表明，在富含葡萄糖的环境中与脂肪细胞共培养，决定了BC细胞转录组的重新编程，驱动脂质积累，这是BC侵袭性的标志，促进干细胞样特性并降低他莫昔芬反应性。此外，我们的数据指出，BC 细胞通过转录效应诱导脂肪细胞脱脂，同时获得多能性增益，作为发生葡萄糖降低时的脂质来源。因此，调节肿瘤周围脂肪细胞的可塑性可能是阻止代谢不平衡患者 BC 进展的关键点。© 2024。作者。

An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality. To explore BC-adipocytes interaction and define the impact of glucose in such dialogue, Mammary Adipose-derived Mesenchymal Stem Cells (MAd-MSCs) were differentiated into adipocytes and co-cultured with ER+ BC cells while exposed to glucose concentration resembling hyperglycemia or normoglycemia in humans (25mM or 5.5mM). The transcriptome of both cell types in co-culture as in mono-culture was profiled by RNA-Seq to define the impact of adipocytes on BC cells and viceversa (i), the action of glucose on BC cells, adipocytes (ii) and their crosstalk (iii). Noteworthy, we provided evidence that co-culture with adipocytes in a glucose-rich environment determined a re-program of BC cell transcriptome driving lipid accumulation, a hallmark of BC aggressiveness, promoting stem-like properties and reducing Tamoxifen responsiveness. Moreover, our data point out to a transcriptional effect through which BC cells induce adipocytes de-lipidation, paralleled by pluripotency gain, as source of lipids when glucose lowering occurs. Thus, modulating plasticity of peri-tumoral adipocytes may represent a key point for halting BC progression in metabolically unbalanced patients.© 2024. The Author(s).