Chetta Paolo, Sriram Renuka, Zadra Giorgia
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA.
Cancers (Basel). 2023 Jul 3;15(13):3473. doi: 10.3390/cancers15133473.
Advanced prostate cancer represents the fifth leading cause of cancer death in men worldwide. Although androgen-receptor signaling is the major driver of the disease, evidence is accumulating that disease progression is supported by substantial metabolic changes. Alterations in de novo lipogenesis and fatty acid catabolism are consistently reported during prostate cancer development and progression in association with androgen-receptor signaling. Therefore, the term "lipogenic phenotype" is frequently used to describe the complex metabolic rewiring that occurs in prostate cancer. However, a new scenario has emerged in which lactate may play a major role. Alterations in oncogenes/tumor suppressors, androgen signaling, hypoxic conditions, and cells in the tumor microenvironment can promote aerobic glycolysis in prostate cancer cells and the release of lactate in the tumor microenvironment, favoring immune evasion and metastasis. As prostate cancer is composed of metabolically heterogenous cells, glycolytic prostate cancer cells or cancer-associated fibroblasts can also secrete lactate and create "symbiotic" interactions with oxidative prostate cancer cells via lactate shuttling to sustain disease progression. Here, we discuss the multifaceted role of lactate in prostate cancer progression, taking into account the influence of the systemic metabolic and gut microbiota. We call special attention to the clinical opportunities of imaging lactate accumulation for patient stratification and targeting lactate metabolism.
晚期前列腺癌是全球男性癌症死亡的第五大主要原因。尽管雄激素受体信号传导是该疾病的主要驱动因素，但越来越多的证据表明，疾病进展是由显著的代谢变化所支持的。在前列腺癌的发生和发展过程中，与雄激素受体信号传导相关，从头脂肪生成和脂肪酸分解代谢的改变一直被报道。因此，“脂肪生成表型”一词经常被用来描述前列腺癌中发生的复杂代谢重编程。然而，一种新的情况出现了，即乳酸可能起主要作用。癌基因/肿瘤抑制因子、雄激素信号传导、缺氧条件以及肿瘤微环境中的细胞的改变可促进前列腺癌细胞中的有氧糖酵解以及肿瘤微环境中乳酸的释放，有利于免疫逃逸和转移。由于前列腺癌由代谢异质性细胞组成，糖酵解的前列腺癌细胞或癌症相关成纤维细胞也可分泌乳酸，并通过乳酸穿梭与氧化型前列腺癌细胞产生“共生”相互作用，以维持疾病进展。在此，我们讨论乳酸在前列腺癌进展中的多方面作用，同时考虑全身代谢和肠道微生物群的影响。我们特别关注通过成像乳酸积累进行患者分层和靶向乳酸代谢的临床机会。
