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 in | Bioconjugate chemistry Vol. 30; no. 10; pp. 2697 - 2702 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
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United States
American Chemical Society
16.10.2019
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| Abstract | 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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| AbstractList | 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. 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.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. |
| Author | Kempson, Ivan M Liao, Zi-Xian Fa, Yu-Chen Tseng, S.-Ja |
| AuthorAffiliation | National Taiwan University Graduate Institute of Oncology Institute of Medical Science and Technology Future Industries Institute National Taiwan University YongLin Scholar |
| AuthorAffiliation_xml | – name: Graduate Institute of Oncology – name: Institute of Medical Science and Technology – name: National Taiwan University – name: National Taiwan University YongLin Scholar – name: Future Industries Institute |
| Author_xml | – sequence: 1 givenname: Zi-Xian orcidid: 0000-0002-3051-0728 surname: Liao fullname: Liao, Zi-Xian organization: Institute of Medical Science and Technology – sequence: 2 givenname: Yu-Chen surname: Fa fullname: Fa, Yu-Chen organization: Institute of Medical Science and Technology – sequence: 3 givenname: Ivan M orcidid: 0000-0002-3886-9516 surname: Kempson fullname: Kempson, Ivan M organization: Future Industries Institute – sequence: 4 givenname: S.-Ja orcidid: 0000-0002-1299-7202 surname: Tseng fullname: Tseng, S.-Ja email: sjatseng@ntu.edu.tw organization: National Taiwan University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31532192$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1155/2010/832454 10.1186/s12885-015-1546-9 10.1021/acsnano.8b02813 10.1073/pnas.1614035114 10.1021/acsnano.8b05893 10.1158/0008-5472.CAN-18-1367 10.1038/ni.2703 10.1038/nature13490 10.1021/bc060382j 10.1021/acs.biomac.9b00020 10.1021/acsnano.6b06051 10.3389/fimmu.2017.00828 10.1038/nature22396 10.1039/C2CC36729G 10.2147/IJN.S144986 10.3324/haematol.2018.191551 10.1097/PPO.0000000000000300 10.1021/acs.bioconjchem.8b00044 10.1080/15384101.2018.1444305 10.1039/C8RA04463E 10.1039/c2cc36589h 10.1371/journal.pone.0087400 10.1016/j.ijcard.2017.07.085 10.1038/ncomms7456 |
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| SubjectTerms | 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 |
| Title | Repolarization of M2 to M1 Macrophages Triggered by Lactate Oxidase Released from Methylcellulose Hydrogel |
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