乳腺癌中代谢重编程的病理生理整合
Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer.
作者信息
Corchado-Cobos Roberto, García-Sancha Natalia, Mendiburu-Eliçabe Marina, Gómez-Vecino Aurora, Jiménez-Navas Alejandro, Pérez-Baena Manuel Jesús, Holgado-Madruga Marina, Mao Jian-Hua, Cañueto Javier, Castillo-Lluva Sonia, Pérez-Losada Jesús
机构信息
Instituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, 37007 Salamanca, Spain.
Instituto de Investigación Biosanitaria de Salamanca (IBSAL), 37007 Salamanca, Spain.
出版信息
Cancers (Basel). 2022 Jan 10;14(2):322. doi: 10.3390/cancers14020322.
Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.
促进肿瘤生长的代谢变化是癌症的标志之一。这些代谢变化的触发因素位于肿瘤实质细胞中,致癌突变在其中引发了增殖的迫切需求,并导致肿瘤的起始和进展。癌细胞在疾病进展过程中会经历显著的代谢重组,以适应其能量需求和不断变化的环境条件。在这种情况下,氧化应激作为触发因素起着至关重要的作用。这些代谢变化是肿瘤细胞与基质肌成纤维细胞相互作用的结果。肿瘤细胞的代谢变化包括蛋白质合成代谢以及细胞膜和核酸的合成,所有这些都促进细胞增殖。它们与基质肌成纤维细胞中的分解代谢和自噬相关联,导致为肿瘤实质细胞释放营养物质。代谢变化导致间质中缺乏葡萄糖和氨基酸等营养物质,并因乳酸而酸化。与缺氧一起,它们会在肿瘤基质的其他细胞(如许多免疫亚群和内皮细胞)中产生功能变化,从而导致肿瘤生长。因此,免疫细胞通过免疫抑制的变化促进组织生长。本综述探讨了乳腺癌中描述的一些代谢变化。