Rizzo Angela Maria, Colombo Irma, Montorfano Gigliola, Zava Stefania, Corsetto Paola Antonia
Department of Pharmacological and Biomolecular Sciences, Università degli studi di Milano, 20122 Milano, Italy.
Cells. 2021 Jan 16;10(1):175. doi: 10.3390/cells10010175.
(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features. (2) Methods: We investigated the peculiar lipid phenotype of a TNBC cell line, MDA-MB-231, and a Luminal A cell line, MCF7, and their different sensitivity to exogenous fatty acids (i.e., palmitic acid (PA) and docosahexaenoic acid (DHA)). Moreover, we verified the impact of exogenous fatty acids on ER lipid composition. (3) Results: The data obtained demonstrate that MDA-MB-231 cells are more sensitive to the lipid microenvironment and that both PA and DHA are able to remodel their ER membranes with consequences on resident enzyme activity. On the contrary, MCF7 cells are less sensitive to PA, whereas they incorporate DHA, although less efficiently than MDA-MB-231 cells. (4) Conclusions: This study sustains the importance of lipid metabolism as an innovative hallmark to discriminate breast cancer subclasses and to develop personalized and innovative pharmacological strategies. The different sensitivities to the lipid environment shown by MCF7 and MDA-MB-231 cells might be related to cell malignancy and chemoresistance onset. In the future, this new approach could lead to a substantial decrease both in deleterious side effects for the patients and in the cost of entire therapeutic treatments coupled with increased therapy efficiency.
（1）背景：脂质代谢是所有肿瘤尤其是乳腺癌的一个基本特征。很少有研究描述影响乳腺癌细胞亚型增殖、侵袭性和治疗效果的不同脂质代谢及其对微环境的敏感性。本研究描述了脂质微环境对具有腔面A型和三阴性乳腺癌（TNBC）特征的两种乳腺癌细胞系内质网（ER）膜及代谢活性的影响。（2）方法：我们研究了TNBC细胞系MDA-MB-231和腔面A型细胞系MCF7独特的脂质表型，以及它们对外源性脂肪酸（即棕榈酸（PA）和二十二碳六烯酸（DHA））的不同敏感性。此外，我们验证了外源性脂肪酸对ER脂质组成的影响。（3）结果：获得的数据表明，MDA-MB-231细胞对脂质微环境更敏感，PA和DHA都能够重塑其ER膜，从而影响驻留酶活性。相反，MCF7细胞对PA不太敏感，尽管其摄取DHA的效率低于MDA-MB-231细胞，但它们能够摄取DHA。（4）结论：本研究支持脂质代谢作为区分乳腺癌亚类以及制定个性化创新药理策略的一个创新特征的重要性。MCF7和MDA-MB-231细胞对脂质环境的不同敏感性可能与细胞恶性程度和化疗耐药性的发生有关。未来，这种新方法可能会大幅降低患者的有害副作用以及整个治疗过程的成本，同时提高治疗效率。
