乳酸，一种驱动肿瘤-基质相互作用的物质。

Lactic acid, a driver of tumor-stroma interactions.

机构信息

Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.

Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China.

出版信息

Int Immunopharmacol. 2022 May;106:108597. doi: 10.1016/j.intimp.2022.108597. Epub 2022 Feb 4.

DOI:10.1016/j.intimp.2022.108597

PMID:35131570

Abstract

Warburg effect is one of the hallmarks of tumor favoring the suppression of normal oxidative phosphorylation (OxPhos) and the adaptation to hypoxia. In addition to providing continuous energy to meet the demands of tumors, acceleratedWarburg effect also producesa large amount of lactic acid. Lactic acid shuttles between different cell populations within the tumor microenvironment (TME) and confers tumor cells to interact with surrounding cells, which has emerged as a new phenomenon in the field of tumor biology and tumorigenesis. Lactic acid not only fulfills the energetic demands of stromal cells, but becomes a major regulator of their activity by serving as a signaling molecule. Activated stromal cells in turn support tumor development. In this review, we discuss the role of lactic acid in transformation and oncogenic function of stromal cells including fibroblasts, macrophages, adipocytes and vascular endothelial cells, and suggest the relevance of lactic acid in therapy response and essential questions in this field.

摘要

瓦博格效应是肿瘤的特征之一，它有利于抑制正常的氧化磷酸化（OxPhos）和适应缺氧。除了提供持续的能量来满足肿瘤的需求外，加速的瓦博格效应还会产生大量的乳酸。乳酸在肿瘤微环境（TME）中的不同细胞群体之间穿梭，并使肿瘤细胞能够与周围细胞相互作用，这在肿瘤生物学和肿瘤发生领域已经成为一个新现象。乳酸不仅满足了基质细胞的能量需求，而且通过作为信号分子成为其活性的主要调节剂。激活的基质细胞反过来又支持肿瘤的发展。在这篇综述中，我们讨论了乳酸在包括成纤维细胞、巨噬细胞、脂肪细胞和血管内皮细胞在内的基质细胞的转化和致癌功能中的作用，并提出了乳酸在治疗反应中的相关性以及该领域的一些重要问题。