Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
Clin Exp Metastasis. 2021 Aug;38(4):343-359. doi: 10.1007/s10585-021-10102-1. Epub 2021 Jun 2.
Metabolic reprogramming is a hallmark of cancer metastasis in which cancer cells manipulate their metabolic profile to meet the dynamic energetic requirements of the tumor microenvironment. Though cancer cell proliferation and migration through the extracellular matrix are key steps of cancer progression, they are not necessarily fueled by the same metabolites and energy production pathways. The two main metabolic pathways cancer cells use to derive energy from glucose, glycolysis and oxidative phosphorylation, are preferentially and plastically utilized by cancer cells depending on both their intrinsic metabolic properties and their surrounding environment. Mechanical factors in the microenvironment, such as collagen density, pore size, and alignment, and biochemical factors, such as oxygen and glucose availability, have been shown to influence both cell migration and glucose metabolism. As cancer cells have been identified as preferentially utilizing glycolysis or oxidative phosphorylation based on heterogeneous intrinsic or extrinsic factors, the relationship between cancer cell metabolism and metastatic potential is of recent interest. Here, we review current in vitro and in vivo findings in the context of cancer cell metabolism during migration and metastasis and extrapolate potential clinical applications of this work that could aid in diagnosing and tracking cancer progression in vivo by monitoring metabolism. We also review current progress in the development of a variety of metabolically targeted anti-metastatic drugs, both in clinical trials and approved for distribution, and highlight potential routes for incorporating our recent understanding of metabolic plasticity into therapeutic directions. By further understanding cancer cell energy production pathways and metabolic plasticity, more effective and successful clinical imaging and therapeutics can be developed to diagnose, target, and inhibit metastasis.
代谢重编程是癌症转移的一个标志，其中癌细胞改变其代谢特征以满足肿瘤微环境的动态能量需求。虽然癌细胞的增殖和穿过细胞外基质的迁移是癌症进展的关键步骤，但它们不一定由相同的代谢物和能量产生途径提供燃料。癌细胞用于从葡萄糖中获得能量的两种主要代谢途径，糖酵解和氧化磷酸化，根据其内在代谢特性和周围环境，优先和塑性地被癌细胞利用。微环境中的机械因素，如胶原蛋白密度、孔径和排列，以及生化因素，如氧气和葡萄糖的可用性，已被证明会影响细胞迁移和葡萄糖代谢。由于癌细胞根据异质的内在或外在因素被鉴定为优先利用糖酵解或氧化磷酸化，因此癌细胞代谢与转移潜能之间的关系是最近的研究热点。在这里，我们综述了在迁移和转移过程中癌细胞代谢的当前体外和体内研究结果，并推断出这项工作的潜在临床应用，通过监测代谢可以帮助诊断和跟踪体内癌症的进展。我们还回顾了目前正在开发的各种代谢靶向抗转移药物的进展情况，包括临床试验和已批准上市的药物，并强调了将我们对代谢可塑性的最新理解纳入治疗方向的潜在途径。通过进一步了解癌细胞的能量产生途径和代谢可塑性，可以开发出更有效和成功的临床成像和治疗方法，以诊断、靶向和抑制转移。
