Repolarization of M2 to M1 Macrophages Triggered by Lactate Oxidase Released from Methylcellulose Hydrogel

Deregulated proliferation of tumors is generally associated with altered energy metabolism. A high rate of anaerobic glycolysis in solid tumors contributes to an acidification of pH to ∼6.7–7.2 in the tumor microenvironment and lactate accumulation. Macrophages in the tumor microenvironment can be e...

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Published inBioconjugate chemistry Vol. 30; no. 10; pp. 2697 - 2702
Main Authors Liao, Zi-Xian, Fa, Yu-Chen, Kempson, Ivan M, Tseng, S.-Ja
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 16.10.2019
Subjects
Acidification
Anticancer properties
Antitumor activity
Depletion
Deregulation
Energy metabolism
Glycolysis
Hydrogels
Lactate oxidase
Lactic acid
Liquid oxygen
Macrophages
Metastases
Methylcellulose
Oxidase
Solid tumors
Tumor cells
Tumors
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Summary:Deregulated proliferation of tumors is generally associated with altered energy metabolism. A high rate of anaerobic glycolysis in solid tumors contributes to an acidification of pH to ∼6.7–7.2 in the tumor microenvironment and lactate accumulation. Macrophages in the tumor microenvironment can be educated by tumor cells. Tumor-derived lactate induces the polarization of M2 macrophages and promotes tumor invasion and metastasis. However, a particular challenge is to sustain lactate depletion. We propose that the repolarization of the tumor-supportive M2 macrophage to the tumor-suppressive M1 macrophage after the depletion of lactate by lactate oxidase (LOX) released from the hydrogels in the tumor microenvironment may enhance the antitumor treatment efficacy.
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ISSN:1043-1802
1520-4812
1520-4812
DOI:10.1021/acs.bioconjchem.9b00618