Lactic acid, a driver of tumor-stroma interactions

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment

Background:

• The Warburg effect is a key metabolic adaptation in tumors, suppressing oxidative phosphorylation (OxPhos) and favoring glycolysis.
• This process leads to significant lactic acid production within the tumor microenvironment (TME).
• Lactic acid is increasingly recognized for its role beyond energy supply, acting as a signaling molecule.

Purpose of the Study:

• To review the multifaceted role of lactic acid in the TME.
• To elucidate how lactic acid influences stromal cell transformation and oncogenic functions.
• To discuss the implications of lactic acid in therapeutic responses.

Main Methods:

• Literature review focusing on metabolic reprogramming in cancer.
• Analysis of studies investigating intercellular communication within the TME.
• Synthesis of current research on lactic acid's signaling capacity.

Main Results:

• Lactic acid produced via the Warburg effect fuels stromal cells (fibroblasts, macrophages, adipocytes, endothelial cells).
• It acts as a signaling molecule, regulating stromal cell activity and promoting tumor development.
• Interactions mediated by lactic acid influence the tumor microenvironment's pro-tumorigenic functions.

Conclusions:

• Lactic acid is a critical mediator in the Warburg effect, influencing stromal cell behavior and tumor progression.
• Understanding lactic acid's role in the TME is essential for developing novel cancer therapies.
• Further research is needed to address key questions regarding lactic acid's therapeutic relevance.