Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth.

Autor: Rivera-Ramos A; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Cruz-Hernández L; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Talaverón R; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Sánchez-Montero MT; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., García-Revilla J; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Mulero-Acevedo M; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Deierborg T; Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, Lund, Sweden., Venero JL; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain., Sarmiento Soto M; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Spain. Electronic address: msarmiento@us.es.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2024 Jun 01; Vol. 591, pp. 216879. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1016/j.canlet.2024.216879
Abstrakt: Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Manuel Sarmiento Soto reports financial support was provided by Ministry of Scientific Research and Innovation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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