Cooperation between T and B cells reinforce the establishment of bone metastases in a mouse model of breast cancer.

Autor: Monteiro AC; Laboratory of Osteo and Tumor Immunology, Department of Immunobiology, Fluminense Federal University, Rio de Janeiro, Brazil; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. Electronic address: anacarolinadossantosmonteiro@id.uff.br., de Andrade Garcia D; Laboratory of Osteo and Tumor Immunology, Department of Immunobiology, Fluminense Federal University, Rio de Janeiro, Brazil; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Du Rocher B; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Fontão APGA; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Nogueira LP; Oral Research Laboratory, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway., Fidalgo G; Laboratory of Applied Physics to Biomedical and Environmental Sciences, Physics Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil., Colaço MV; Laboratory of Applied Physics to Biomedical and Environmental Sciences, Physics Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil., Bonomo A; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Brazil; Research Network on Neuroinflammation (RENEURIN), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Bone [Bone] 2024 Jan; Vol. 178, pp. 116932. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1016/j.bone.2023.116932
Abstrakt: Immune cells educated by the primary breast tumor and their secreted factors support the formation of bone pre-metastatic niche. Indeed, we showed that RANKL + CD3 + T cells, specific for the 4T1 mammary carcinoma cell line, arrive at the bone marrow before metastatic cells and set the pre-metastatic niche. In the absence of RANKL expressed by T cells, there is no pre-metastatic osteolytic disease and bone metastases are completely blocked. Adding to the role of T cells, we have recently demonstrated that dendritic cells assist RANKL + T cell activities at bone pre-metastatic niche, by differentiating into potent bone resorbing osteoclast-like cells, keeping their antigen-presenting cell properties, providing a positive feedback loop to the osteolytic profile. Here we are showing that bone marrow-derived CD19 + B cells, from 4T1 tumor-bearing mice, also express the pro-osteoclastogenic cytokine receptor activator of NFκB ligand (RANKL). Analysis of trabecular bone mineral density by conventional histomorphometry and X-ray microtomography (micro-CT) demonstrated that B cells expressing RANKL cooperate with 4T1-primed CD3 + T cells to induce bone loss. Moreover, RANKL expression by B cells depends on T cells activity, since experiments performed with B cells derived from 4T1 tumor-bearing nude BALB/c mice resulted in the maintenance of trabecular bone mass instead of bone loss. Altogether, we believe that 4T1-primed RANKL + B cells alone are not central mediators of bone loss in vivo but when associated with T cells induce a strong decrease in bone mass, accelerating both breast cancer progression and bone metastases establishment. Although several studies performed in different pathological settings, showed that B cells, positively and negatively impact on osteoclastogenesis, due to their capacity to secret pro or anti-osteoclastogenic cytokines, as far as we know, this is the first report showing the role of RANKL expression by B cells on breast cancer-derived bone metastases scenario.
Competing Interests: Declaration of competing interest The authors state that they have no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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