Cellular Plasticity in Prostate Cancer Bone Metastasis

Figure 2

Cellular plasticity of prostate cancer cells over time. The plasticity of cancer cells over time can be delineated from experimental animal and in vitro models. Cells in the primary tumour undergo EMT, which enhances their migratory and invasive potential. These invasive cells enter the circulation and may exist as mesenchymal, epithelial, or semimesenchymal/semiepithelial circulating tumour cells (CTCs). Extravasation of CTCs into the bone gives rise to micrometastases. As the metastatic tumour cells colonise the bone and grow into macrometastasis, cells within the tumour centre undergo MET to enable tumour growth and survival under hypoxia, while cells at the invasive edge retain their mesenchymal phenotype to enable invasiveness and osteomimicry. It is suggested that these phenotypic changes are partial and that metastatic cells can dynamically transition between these two states to allow for adaptation to altered microenvironmental stimuli and for further invasion and secondary dissemination. Clinical samples, on the other hand, represent observations of established primary masses and macrometastases at static points in time. Therefore, they cannot capture the dynamic nature of cellular plasticity. Furthermore, current CTC-detection techniques are epithelial-based and cannot capture CTCs that are mostly mesenchymal and have reduced expression of epithelial markers, which would result in missing a significant fraction of CTCs that are predominantly in the mesenchymal state.