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• W4387521208 endingPage "116932" @default.
• W4387521208 startingPage "116932" @default.
• W4387521208 abstract "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." @default.
• W4387521208 created "2023-10-12" @default.
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• W4387521208 date "2023-10-01" @default.
• W4387521208 modified "2023-10-15" @default.
• W4387521208 title "Cooperation between T and B cells reinforce the establishment of bone metastases in a mouse model of breast cancer" @default.
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• W4387521208 doi "https://doi.org/10.1016/j.bone.2023.116932" @default.
• W4387521208 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37832903" @default.
• W4387521208 hasPublicationYear "2023" @default.
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