Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis
| Autor: | Gemma Di Pompo, Costantino Errani, Robert Gillies, Laura Mercatali, Toni Ibrahim, Jacopo Tamanti, Nicola Baldini, Sofia Avnet |
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| Přispěvatelé: | Di Pompo G., Errani C., Gillies R., Mercatali L., Ibrahim T., Tamanti J., Baldini N., Avnet S. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Osteolysis QH301-705.5 interleukin 6 interleukin 8 Bone remodeling Proinflammatory cytokine Cell and Developmental Biology tocilizumab Osteoclast medicine bone metastasi Biology (General) intratumoral acidosis Interleukin 6 Original Research bone metastasis cancer microenvironment biology business.industry Bone metastasis osteoblasts intratumoral acidosi Cell Biology medicine.disease medicine.anatomical_structure osteoclasts RANKL osteoclast Cancer research biology.protein osteoblast Tumor necrosis factor alpha business Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology Frontiers in Cell and Developmental Biology, Vol 9 (2021) |
| Popis: | Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast–osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM. |
| Databáze: | OpenAIRE |
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