Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth
(2024) In Cancer Letters 591.- Abstract
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... (More)
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.
(Less)
- author
- Rivera-Ramos, Alberto ; Cruz-Hernández, Luis ; Talaverón, Rocío ; Sánchez-Montero, María Teresa ; García-Revilla, Juan LU ; Mulero-Acevedo, Marta ; Deierborg, Tomas LU ; Venero, José Luis and Sarmiento Soto, Manuel
- organization
- publishing date
- 2024-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Brain metastasis, Galectin-3, Glioblastoma, Microglia, Tumour-associated microglia and macrophages (TAMs)
- in
- Cancer Letters
- volume
- 591
- article number
- 216879
- publisher
- Elsevier
- external identifiers
-
- scopus:85190973862
- pmid:38636895
- ISSN
- 0304-3835
- DOI
- 10.1016/j.canlet.2024.216879
- language
- English
- LU publication?
- yes
- id
- dd14fd67-3699-4afa-9de0-244cce783369
- date added to LUP
- 2024-05-07 14:43:03
- date last changed
- 2024-05-21 16:44:24
@article{dd14fd67-3699-4afa-9de0-244cce783369,
abstract = {{<p>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.</p>}},
author = {{Rivera-Ramos, Alberto and Cruz-Hernández, Luis and Talaverón, Rocío and Sánchez-Montero, María Teresa and García-Revilla, Juan and Mulero-Acevedo, Marta and Deierborg, Tomas and Venero, José Luis and Sarmiento Soto, Manuel}},
issn = {{0304-3835}},
keywords = {{Brain metastasis; Galectin-3; Glioblastoma; Microglia; Tumour-associated microglia and macrophages (TAMs)}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Cancer Letters}},
title = {{Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth}},
url = {{http://dx.doi.org/10.1016/j.canlet.2024.216879}},
doi = {{10.1016/j.canlet.2024.216879}},
volume = {{591}},
year = {{2024}},
}