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The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages
- Title
- The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages
- Authors
- Vadevoo, Sir Murugan Poongkavithai; Gunassekaran, Gowri Rangaswarmy; Lee, ChaeEun; Lee, NaHye; Lee, Jiyoun; Chae, Sehyun; Park, Jae-Yong; Koo, JaeHyung; Lee, Byungheon
- DGIST Authors
- Vadevoo, Sir Murugan Poongkavithai; Gunassekaran, Gowri Rangaswarmy; Lee, ChaeEun; Lee, NaHye; Lee, Jiyoun; Chae, Sehyun; Park, Jae-Yong; Koo, JaeHyung; Lee, Byungheon
- Issue Date
- 2021-09
- Citation
- Proceedings of the National Academy of Sciences of the United States of America, 118(37)
- Type
- Article
- Author Keywords
- TAMs; GPCR; Lactate; Olfr78; OR51E2
- Keywords
- PROTEIN-COUPLED RECEPTORS; OLFACTORY RECEPTOR; ACTIVATION; POLARIZATION; EXPRESSION; DEPLETION; TARGETS; GROWTH; GENE; G2A
- ISSN
- 0027-8424
- Abstract
- Expression and function of odorant receptors (ORs), which account for more than 50% of G protein-coupled receptors, are being increasingly reported in nonolfactory sites. However, ORs that can be targeted by drugs to treat diseases remain poorly identified. Tumorderived lactate plays a crucial role in multiple signaling pathways leading to generation of tumor-associated macrophages (TAMs). In this study, we hypothesized that the macrophage OR Olfr78 functions as a lactate sensor and shapes the macrophage-tumor axis. Using Olfr78+/+ and Olfr78-/- bone marrow-derived macrophages with or without exogenous Olfr78 expression, we demonstrated that Olfr78 sensed tumor-derived lactate, whichwas themain factor in tumor-conditioned media responsible for generation of protumoral M2-TAMs. Olfr78 functioned together with Gpr132 to mediate lactate-induced generation of protumoral M2-TAMs. In addition, syngeneic Olfr78-deficient mice exhibited reduced tumor progression and metastasis together with an increased anti- versus protumoral immune cell population. We propose that the Olfr78-lactate interaction is a therapeutic target to reduce and prevent tumor progression and metastasis. © 2021 National Academy of Sciences. All rights reserved.
- URI
- http://hdl.handle.net/20.500.11750/15460
- DOI
- 10.1073/pnas.2102434118
- Publisher
- National Academy of Sciences
- Related Researcher
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Koo, JaeHyung
Brain-Immune Axis Laboratory
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Research Interests
장내미생물/감염균 유래 대사체를 통한 신경염증, 알츠하이머병, 우울증, 당뇨/비만, 대사체/수용체 상호작용에 의한 대사연구
- Files:
There are no files associated with this item.
- Collection:
- Department of New BiologyBrain-Immune Axis Laboratory1. Journal Articles
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