ArticleGenes & genomics2025
Lactate released by lung adenocarcinoma (LUAD) cells promotes M2 macrophage polarization via the GPR132/cAMP/PKA pathway.
Article in Genes & genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Review
- Macrophages in lung cancer: principal factors, regulatory mechanisms, and therapeutic opportunities: a narrative review.Translational lung cancer research · 2026Review
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
- The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets.Frontiers in immunology · 2026Review
- FOXP1 transcriptionally activates NUSAP1 to induce M2 polarization of tumor-associated macrophages via glycolysis in hepatocellular carcinoma.Frontiers in genetics · 2026Article
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Authors and funding
3 authors.
Funding
Abstract
backgroundIncreasing evidence suggests that lactate is an essential compound in the tumor microenvironment, and especially for macrophage cells. However, the mechanism by which lactate affects macrophages remains unclear.
objectiveThis study investigated whether and how lactate affects macrophage polarization in lung adenocarcinoma (LUAD).
methodsClinical samples of LUAD and paracancerous tissue were obtained for evaluation of lactate dehydrogenase A (LDHA) expression. LUAD cell lines and THP-1 induced macrophages were used in this study. Quantitative real-time PCR (QPCR), western blotting, and immunohistochemical (IHC) staining were performed to detect gene expression. Flow cytometry and ELISA assays were used to detect the levels of M1 macrophage and M2 macrophage biomarkers.
resultsLDHA was highly expressed in the LUAD tissues. Culture medium supernatants derived from LUAD cells (CM) promoted macrophage M2 polarization, and lactate levels were elevated in the CM. Inhibition of LDHA in LUAD cells decreased lactate levels and suppressed M2 macrophage polarization. Moreover, overexpression of GPR132 in macrophages promoted, while GPR132 knockdown in macrophages suppressed M2 macrophage polarization and cAMP (Cyclic Adenosine 3',5'-Monophosphate)/PKA (Protein Kinase) pathway activation induced by lactate. The effect of GPR132 overexpression was reversed by a PKA inhibitor (H-89).
conclusionCollectively, our results confirmed that lactate released by LUAD cells promoted M2 macrophage polarization via the GPR132/cAMP/PKA pathway.
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