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The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages

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dc.contributor.authorVadevoo, Sri Murugan Poongkavithai-
dc.contributor.authorGunassekaran, Gowri Rangaswamy-
dc.contributor.authorLee, ChaeEun-
dc.contributor.authorLee, NaHye-
dc.contributor.authorLee, Jiyoun-
dc.contributor.authorChae, Sehyun-
dc.contributor.authorPark, Jae-Yong-
dc.contributor.authorKoo, JaeHyung-
dc.contributor.authorLee, Byungheon-
dc.date.accessioned2023-08-16T09:31:15Z-
dc.date.available2023-08-16T09:31:15Z-
dc.date.created2022-01-11-
dc.date.issued2021-09-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/302-
dc.description.abstractExpression 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, which was the main 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.-
dc.language영어-
dc.language.isoen-
dc.publisherNATL ACAD SCIENCES-
dc.titleThe macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages-
dc.typeArticle-
dc.contributor.affiliatedAuthorChae, Sehyun-
dc.identifier.doi10.1073/pnas.2102434118-
dc.identifier.scopusid2-s2.0-85114726952-
dc.identifier.wosid000697000500012-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.118, no.37-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.citation.titlePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.citation.volume118-
dc.citation.number37-
dc.type.rimsART-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaScience & Technology - Other Topics-
dc.relation.journalWebOfScienceCategoryMultidisciplinary Sciences-
dc.subject.keywordPlusPROTEIN-COUPLED RECEPTORS-
dc.subject.keywordPlusOLFACTORY RECEPTOR-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusPOLARIZATION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusDEPLETION-
dc.subject.keywordPlusTARGETS-
dc.subject.keywordPlusGROWTH-
dc.subject.keywordPlusGENE-
dc.subject.keywordPlusG2A-
dc.subject.keywordAuthorGPCR-
dc.subject.keywordAuthorOlfr78-
dc.subject.keywordAuthorTAMs-
dc.subject.keywordAuthorOR51E2-
dc.subject.keywordAuthorlactate-
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