ArticleMolecular cancer2014
Direct but not indirect co-culture with osteogenically differentiated human bone marrow stromal cells increases RANKL/OPG ratio in human breast cancer cells generating bone metastases.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 32 citations in OpenAlex.
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review).International journal of oncology · 2025Review
- Role and mechanism of botanical drugs and their metabolites in osteoporosis: new strategies for clinical application.Frontiers in pharmacology · 2025Review
- 2D and 3D In Vitro Co-culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.Journal of translational medicine · 2024Review
- Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- The Contribution of the Immune System in Bone Metastasis Pathogenesis.International journal of molecular sciences · 2019Review
- 2D and 3D In Vitro Co-Culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Bioprinting and Organ-on-Chip Applications Towards Personalized Medicine for Bone Diseases.Stem cell reviews and reports · 2017Review
- Breast cancer cells and bone marrow mesenchymal stromal cells: a regulated modulation of the breast tumor in the context of immune response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Transition into inflammatory cancer-associated adipocytes in breast cancer microenvironment requires microRNA regulatory mechanism.PloS one · 2017Article
- Cancer Cell Colonisation in the Bone Microenvironment.International journal of molecular sciences · 2016Review
- In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone.International journal of molecular sciences · 2016Review
- Progress towards understanding heterotypic interactions in multi-culture models of breast cancer.Integrative biology : quantitative biosciences from nano to macro · 2016Review
- Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ.Experimental and therapeutic medicine · 2016Article
- Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions.Clinical & experimental metastasis · 2015Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone metastases arise in nearly 70% of patients with advanced breast cancer, but the complex metastatic process has not been completely clarified yet. RANKL/RANK/OPG pathway modifications and the crosstalk between metastatic cells and bone have been indicated as potential drivers of the process. Interactions between tumor and bone cells have been studied in vivo and in vitro, but specific effects of the direct contact between human metastatic cells and human bone cells on RANKL/RANK/OPG pathway have not been investigated.
findingsWe directly co-cultured bone metastatic human breast cancer cells (BOKL) with osteo-differentiated human mesenchymal cells (BMSCs) from 3 different donors. BMSCs and BOKL were then enzymatically separated and FACS sorted. We found a significant increase in the RANKL/OPG ratio as compared to control, which was not observed in BOKL cultured in medium conditioned by BMSCs, neither in BOKL directly cultured with fibroblasts or medium conditioned by fibroblasts. Direct co-culture with osteo-differentiated BMSCs caused BOKL aggregation while proliferation was not affected by co-culture. To more specifically associate RANKL expression to osteogenic differentiation degree of BMSCs, we determined their osteogenic markers expression and matrix calcification relative to osteoblasts and fibroblasts.
conclusionsIn conclusion, our co-culture model allowed to demonstrate for the first time that direct contact but not paracrine interactions between human metastatic breast cancer cells and bone cells has a significant effect on RANKL/OPG expression in bone metastatic cells. Furthermore, only direct contact with the bone microenvironment induced BOKL clustering without however significantly influencing their proliferation and migration.
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