4.7 Article

Lactic acid, a driver of tumor-stroma interactions

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 106, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2022.108597

Keywords

Lactic acid; Tumor-associated fibroblasts; Tumor-associated macrophages; Tumor-associated adipocytes; Tumor-associated vascular endothelial cells

Funding

  1. Natural Science Foun-dation of Hunan Province [2019JJ40251]
  2. Open Fund of Hunan Provincial Key Laboratory of Novel Antibody-Based Drug and its Intel-ligent Transport System [2020TP1044]
  3. Reform and Development Fund of Hunan Colleges and Universities [202185]
  4. Undergraduate Training Program for Innovation and Entrepreneurship of Hunan Province [2575, 2756]

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Lactic acid plays a crucial role in the transformation and oncogenic function of stromal cells in the tumor microenvironment. It not only provides energy for stromal cells but also acts as a signaling molecule to regulate their activity. Activated stromal cells, in turn, support tumor development.
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, accelerated Warburg effect also produces a 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.

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