Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells

Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tu...

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Bibliographic Details
Published in:Cancer cell international 2021-09, Vol.21 (1), p.1-479, Article 479
Main Authors: Li, Xiao, Zhu, Hongming, Sun, Weixuan, Yang, Xingru, Nie, Qing, Fang, Xuedong
Format: Article
Language:English
Subjects:
Amino acids
Ammonia
Cancer
Cancer cells
Cancer therapies
Cancer-associated fibroblasts
Cell growth
Cytokines
Enzymes
Fibroblasts
Glutamine
Kinases
Lung cancer
Metabolism
Metabolites
Metastases
Metastasis
MicroRNAs
Nitrogen
Review
Stroma
Tumor microenvironment
Tumors
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Summary:Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a “nitrogen reservoir” for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism.
ISSN:1475-2867
1475-2867
DOI:10.1186/s12935-021-02121-5