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Published (Version of Record)CC BY V4.0, Open Access
Journal article
Maraviroc prevents HCC development by suppressing macrophages and the liver progenitor cell response in a murine chronic liver disease model
Cancers, Vol.13(19), Article 4935
2021
Abstract
Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms. MVC reduced LPC numbers in CDE mice by 54%, with a smaller reduction seen in macrophages. Transcript and protein abundance of LPC-associated markers correlated with this reduction. The CDE diet activated phosphorylation of AKT and STAT3 and was inhibited by MVC. LPCs did not express Ccr5 in our model; in contrast, macrophages expressed high levels of this receptor, suggesting the effect of MVC is mediated by targeting macrophages. MVC reduced CD45+ cells and macrophage migration in liver and blocked the CDE-induced transition of liver macrophages from an M1- to M2-tumour-associated macrophage (TAM) phenotype. These findings suggest MVC has potential as a re-purposed therapeutic agent for treating chronic liver diseases where M2-TAM and LPC numbers are increased, and the incidence of HCC is enhanced.
Details
- Title
- Maraviroc prevents HCC development by suppressing macrophages and the liver progenitor cell response in a murine chronic liver disease model
- Authors/Creators
- A.M. Passman (Author/Creator) - Harry Perkins Institute of Medical ResearchR.P. Strauss (Author/Creator) - Harry Perkins Institute of Medical ResearchS.B. McSpadden (Author/Creator) - Harry Perkins Institute of Medical ResearchM. Finch-Edmondson (Author/Creator) - Harry Perkins Institute of Medical ResearchN. Andrewartha (Author/Creator) - Harry Perkins Institute of Medical ResearchK.H. Woo (Author/Creator) - Harry Perkins Institute of Medical ResearchL.A. Diepeveen (Author/Creator) - Harry Perkins Institute of Medical ResearchW. Zhao (Author/Creator) - The University of Western AustraliaJ. Fernández-Irigoyen (Author/Creator) - NavarrabiomedE. Santamaría (Author/Creator) - NavarrabiomedL. Medina-Ruiz (Author/Creator) - University of GlasgowM. Szpakowska (Author/Creator) - Luxembourg Institute of HealthA. Chevigné (Author/Creator) - Luxembourg Institute of HealthH. Park (Author/Creator) - Harry Perkins Institute of Medical ResearchR. Carlessi (Author/Creator) - Curtin UniversityJ.E.E. Tirnitz-Parker (Author/Creator) - Curtin UniversityJ.R. Blanco (Author/Creator) - Center for Biomedical Research of La RiojaR. London (Author/Creator) - Harry Perkins Institute of Medical ResearchB.A. Callus (Author/Creator) - Murdoch UniversityC.L. Elsegood (Author/Creator) - The University of Western AustraliaM.V. Baker (Author/Creator) - The University of Western AustraliaA. Martínez (Author/Creator)G.C.T. Yeoh (Author/Creator) - The University of Western AustraliaL. Ochoa-Callejero (Author/Creator) - Center for Biomedical Research of La Rioja
- Publication Details
- Cancers, Vol.13(19), Article 4935
- Publisher
- MDPI
- Identifiers
- 991005540042207891
- Copyright
- © 2021 by the authors
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.102 Stem Cell Research
- 1.102.1150 Hepatocyte Growth Factor
- Web Of Science research areas
- Oncology
- ESI research areas
- Clinical Medicine