Molecular Disease Mechanisms Group, Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belval, Luxembourg.
Tumor Stroma Interaction Group, Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090 Vienna, Austria.
Cells. 2021 Feb 2;10(2):304. doi: 10.3390/cells10020304.
Metabolism is considered to be the core of all cellular activity. Thus, extensive studies of metabolic processes are ongoing in various fields of biology, including cancer research. Cancer cells are known to adapt their metabolism to sustain high proliferation rates and survive in unfavorable environments with low oxygen and nutrient concentrations. Hence, targeting cancer cell metabolism is a promising therapeutic strategy in cancer research. However, cancers consist not only of genetically altered tumor cells but are interwoven with endothelial cells, immune cells and fibroblasts, which together with the extracellular matrix (ECM) constitute the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are linked to poor prognosis in different cancer types, are one important component of the TME. CAFs play a significant role in reprogramming the metabolic landscape of tumor cells, but how, and in what manner, this interaction takes place remains rather unclear. This review aims to highlight the metabolic landscape of tumor cells and CAFs, including their recently identified subtypes, in different tumor types. In addition, we discuss various in vitro and in vivo metabolic techniques as well as different in silico computational tools that can be used to identify and characterize CAF-tumor cell interactions. Finally, we provide our view on how mapping the complex metabolic networks of stromal-tumor metabolism will help in finding novel metabolic targets for cancer treatment.
新陈代谢被认为是所有细胞活动的核心。因此，包括癌症研究在内的各个生物学领域都在对代谢过程进行广泛研究。众所周知，癌细胞会调整其代谢以维持高增殖率，并在低氧和低营养浓度的不利环境中存活。因此，针对癌细胞代谢是癌症研究中一种很有前途的治疗策略。然而，癌症不仅由遗传改变的肿瘤细胞组成，而且与内皮细胞、免疫细胞和成纤维细胞交织在一起，这些细胞与细胞外基质（ECM）一起构成了肿瘤微环境（TME）。癌症相关成纤维细胞（CAFs）与不同癌症类型的预后不良有关，是 TME 的一个重要组成部分。CAFs 在重新编程肿瘤细胞的代谢景观方面发挥着重要作用，但这种相互作用是如何发生的，以及以何种方式发生，目前还不是很清楚。这篇综述旨在强调不同肿瘤类型中肿瘤细胞和 CAFs 的代谢景观，包括它们最近确定的亚型。此外，我们还讨论了可用于识别和表征 CAF-肿瘤细胞相互作用的各种体外和体内代谢技术以及不同的计算工具。最后，我们提供了我们的观点，即绘制基质-肿瘤代谢的复杂代谢网络将如何帮助寻找癌症治疗的新代谢靶点。
