Metabolism & Nutrition Research Group, Louvain Drug Research Institute, WELBIO (Walloon Excellence in Life sciences and BIOtechnology), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
Biomedical Magnetic Resonance Research Group, UCLouvain, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
J Cell Mol Med. 2020 Sep;24(17):10233-10244. doi: 10.1111/jcmm.15639. Epub 2020 Jul 17.
Epidemiological studies have shown that obese subjects have an increased risk of developing triple-negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high-fat diet in TNBC tumour-bearing mice significantly increased tumour growth. By showing no effect of high-fat diet in obesity-resistant mice, we demonstrated the necessity to develop obesity-related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity-related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.
流行病学研究表明,肥胖患者发生三阴性乳腺癌(TNBC)的风险增加,整体存活率降低。然而,肥胖与 TNBC 之间的关系仍难以理解。我们假设脂联素是一种在肥胖中水平升高的脂肪因子,可能是导致 TNBC 肥胖患者肿瘤生长和转移的主要因素。我们观察到,高脂肪饮食诱导的肥胖会显著促进 TNBC 荷瘤小鼠的肿瘤生长。通过在肥胖抵抗小鼠中观察到高脂肪饮食没有影响,我们证明了需要发展与肥胖相关的疾病以增加肿瘤生长。肥胖小鼠的皮下脂肪组织和肿瘤中脂联素 mRNA 的表达也增加了。我们进一步强调,在瘦小鼠中复制与肥胖相关的脂联素水平会导致 TNBC 生长和脑转移的形成增加。最后,向肥胖小鼠注射脂联素能拮抗剂 F13A 可显著抑制 TNBC 生长,表明脂联素能系统干扰可能是肥胖和 TNBC 背景下一种有趣的治疗策略。