The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone.
The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone.
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DOI：
10.1007/s11914-018-0453-9
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发表时间：
2018-08
影响因子：
4.3
通讯作者：
Podgorski I
中科院分区：
文献类型：
--
作者：
Diedrich JD;Herroon MK;Rajagurubandara E;Podgorski I
近年来，骨髓脂肪细胞已成为骨转移进展的关键贡献者。在这篇综述中，我们特别关注它们作为脂质供应者的作用，并讨论与脂质代谢密切相关的促生存途径，受脂肪细胞-肿瘤细胞相互作用的影响，并可能影响肿瘤细胞在骨髓空间中茁壮成长并逃避治疗的能力。计算机模拟、临床前和临床证据表明，在富含脂肪细胞的组织（如骨髓）中，肿瘤细胞依赖外源性脂质调节细胞能量学并适应转移性小生境的苛刻代谢条件。脂肪细胞提供的脂质具有通过调节糖酵解和呼吸、脂肪酸氧化、脂质去饱和和PPAR信号传导来改变细胞的代谢决定的潜力。脂质信号传导对线粒体稳态的下游作用最终控制生与死的决定，提供了获得生存优势和降低对治疗敏感性的机制。未来的研究需要确定调节肿瘤对外源性脂质依赖性的关键代谢和信号传导途径，从而驱动骨髓生态位中的促生存行为。
Bone marrow adipocytes have emerged in recent years as key contributors to metastatic progression in bone. In this review, we focus specifically on their role as the suppliers of lipids and discuss pro-survival pathways that are closely linked to lipid metabolism, affected by the adipocyte-tumor cell interactions, and likely impacting the ability of the tumor cell to thrive in bone marrow space and evade therapy. The combined in silico, pre-clinical, and clinical evidence shows that in adipocyte-rich tissues such as bone marrow, tumor cells rely on exogenous lipids for regulation of cellular energetics and adaptation to harsh metabolic conditions of the metastatic niche. Adipocyte-supplied lipids have a potential to alter the cell’s metabolic decisions by regulating glycolysis and respiration, fatty acid oxidation, lipid desaturation, and PPAR signaling. The downstream effects of lipid signaling on mitochondrial homeostasis ultimately control life vs. death decisions, providing a mechanism for gaining survival advantage and reduced sensitivity to treatment. There is a need for future research directed towards identifying the key metabolic and signaling pathways that regulate tumor dependence on exogenous lipids and consequently drive the pro-survival behavior in the bone marrow niche.
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