Prostate cancer is the second most common cancer worldwide for males. The available treatments consist in surgical removal coupled with radio-/chemo-therapy. Prostate cancer metastasises mainly in bone, causing significant increase of clinical morbidity and mortality. Bone metastases develop from a small fraction of the cells shredded by the primary tumour into the blood stream. These cells are able to invade the bone and form metastatic lesions. We aim to uncover the molecular traits characterising these cells thus to predict the risk of bone metastases. Using an in vitro co-culture system of osteotropic prostate cancer cells and human osteoblasts, we investigated the interaction between cancer cells and bone microenvironment. We used flow cytometry to investigate the changes in cell cycle at various time points during the co-culture (24 h, 48 h, 96 h). Moreover, we applied to state-of-the-art single cell technologies to analyse the expression of target genes and resolve the population composition at a single cell level. Upon co-culture, prostate cancer cells showed progressively increasing proliferation. We also observed significant changes in the subpopulation distribution amongst prostate cancer cells, with genes such as ALDH7A1 and cKit, differentially expressed between co-cultured cells and controls. Dissecting the tumour heterogeneity in the early events of bone colonisation and metastases formation will allow the development of new diagnostic and curative approaches oriented towards personalised therapy.
Disclosure: The authors declared no competing interests. Marie Curie Initial Training Network Bone-Net Grant number: 264817.