脂肪细胞分泌物对代表四大乳腺癌亚型的乳腺癌细胞系的特定代谢指纹的影响。
The Influence of Adipocyte Secretome on Selected Metabolic Fingerprints of Breast Cancer Cell Lines Representing the Four Major Breast Cancer Subtypes.
发表日期:2023 Aug 22
作者:
Carla Luís, Bárbara Guerra-Carvalho, Patrícia C Braga, Carla Guedes, Emília Patrício, Marco G Alves, Ruben Fernandes, Raquel Soares
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
分子亚型(MS)是乳腺癌(BC)最常用的分类之一。根据雌激素、孕激素和HER2的受体表达,广泛接受四种MS。脂肪组织对BC MS代谢障碍的影响仍不清楚。本研究旨在阐明不同MS的乳腺癌细胞系在脂肪细胞相关因子作用下的代谢改变。从人体皮下脂肪组织中分离出成赘肉前体细胞,分化为成熟的脂肪细胞。将MS代表性细胞系暴露于成熟的脂肪细胞细胞外分泌物。收集细胞外液进行代谢组学分析,并提取RNA进行RT-PCR评估酶表达。脂肪细胞细胞外分泌物暴露导致华氏效应速率下降和胆固醇释放增加。与Luminal A(MCF-7)和三阴性(TN)(MDA-MB-231)细胞系相比,HER2+细胞系(BT-474和SK-BR-3)表现出类似的代谢模式,前者呈现相同的代谢。Luminal A和TN的代表性细胞系被发现具有部分补充反应,而HER2+细胞系可能出现向外消耗反应。我们的结果表明脂肪细胞细胞外分泌物在不同BC MS代表性细胞系中对中心代谢产生不同的影响。
Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.