The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells.

IF 3.5 4区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Adipocyte Pub Date : 2021-12-01 DOI:10.1080/21623945.2021.1979758
Ilze Mentoor, Anna-Mart Engelbrecht, Mari van de Vyver, Paul J van Jaarsveld, Theo Nell
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引用次数: 5

Abstract

Adipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the underlying treatment resistance mechanisms. Cell-viability assays, and Western blots were performed to determine alterations in apoptotic, proliferation and lipid metabolism protein markers. Free fatty acids (FFA) and inflammatory markers in the collected treatment-conditioned media were also quantified. Adipocyte secretory factors increased the cell-viability of doxorubicin-treated cells (p < 0.0001), which did not correspond to apoptosis or proliferation pathways. Adipocyte secretory factors increased the protein expression of hormone-sensitive lipase (p < 0.05) in doxorubicin-treated cells. Adipocyte secretory factors increased the utilization of leptin (p < 0.05) and MCP-1 (p < 0.01) proteins and possibly inhibited release of linoleic acid by doxorubicin-treated cells (treatment-conditioned media FFA profiles). Adipocyte secretory factors induced doxorubicin treatment resistance, by increasing the utilization of inflammatory mediators and inhibiting the release of FFA by doxorubicin-treated cells. This further promotes inflammation and lipid metabolic reprogramming (lipid storage) in the tumour microenvironment, which breast cancer cells use to evade the toxic effects induced by doxorubicin and confers to acquired treatment resistance.

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脂肪细胞对阿霉素处理的三阴性乳腺癌细胞脂质代谢的旁分泌作用。
乳腺肿瘤微环境中的脂肪细胞促进获得性治疗抵抗。我们使用体外脂肪细胞条件培养基方法研究脂肪细胞分泌因子对阿霉素治疗的MDA-MB-231乳腺癌细胞的直接旁分泌作用,以阐明潜在的治疗耐药机制。细胞活力测定和Western blots检测凋亡、增殖和脂质代谢蛋白标志物的变化。收集的治疗条件培养基中的游离脂肪酸(FFA)和炎症标志物也被量化。脂肪细胞分泌因子增加了阿霉素处理细胞的细胞活力(p < 0.0001),这与凋亡或增殖途径不一致。脂肪细胞分泌因子增加了阿霉素处理细胞中激素敏感脂肪酶的蛋白表达(p < 0.05)。脂肪细胞分泌因子增加了瘦素(p < 0.05)和MCP-1 (p < 0.01)蛋白的利用,并可能抑制阿霉素处理的细胞释放亚油酸(处理条件培养基FFA谱)。脂肪细胞分泌因子通过增加炎症介质的利用和抑制阿霉素处理的细胞释放FFA来诱导阿霉素治疗抵抗。这进一步促进了肿瘤微环境中的炎症和脂质代谢重编程(脂质储存),乳腺癌细胞利用这些重编程来逃避阿霉素诱导的毒性作用,并导致获得性治疗耐药性。
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来源期刊
Adipocyte
Adipocyte Medicine-Histology
CiteScore
6.50
自引率
3.00%
发文量
46
审稿时长
32 weeks
期刊介绍: Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.
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