Multi-omics qualification of an organ-on-a-chip model of osteolytic bone metastasis

This study developed a unique organ-on-a-chip model to simulate osteolytic bone metastasis and utilised a multiomics approach for characterisation/qualification and validation against in vivo data. Using the Emulate S1 platform, we co-cultured murine osteocytes and osteoclasts to recreate the bone microenvironment and combined with breast cancer cells in a separate channel separated by a porous membrane. Using RNA sequencing, cytokine profiling, and fluorescence staining, we demonstrated the importance of the complete tri-culture model in replicating in vivo biology, and uncovered critical pathways involved in metastasis. A synergistic effect was observed in the tri-culture organ-chip model, leading to increased cancer cell migration and the upregulation of pro-metastatic and pro-inflammatory pathways that promote bone degradation and cancer progression. This study validates an organ-chip model of osteolytic breast cancer bone metastasis as a scalable alternative to traditional animal models. Furthermore, we show how multi-omics and bioinformatics may be used for qualification and validation of organ-chip models; for unpicking the relative contribution of the different cell types; and to identify signalling pathways and therapeutic targets. Organ-on-a-chip models of osteolytic breast cancer metastasis to bone (Bulk RNAseq of Chips 1-6)