Fig. 6 ∣. Interactions between tumour cells and stroma shape the evolutionary dynamics of PCa and drive overall tumour aggressiveness.

Growth factor signalling is essential to both tumour and reactive stroma. Limited availability of growth factors leads to an increased competition between tumour and stromal cells. This competition results in slower tumour growth (lower risk estimation) but also increased selection and more rapid evolution (leading to a more heterogeneous population). In contrast, where growth factor availability is not limiting, there are more mutualistic interactions between tumour and stroma. This situation results in faster growing tumours (higher risk estimation) but, paradoxically, weaker selection pressure leading to less aggressive tumour cells (and a less heterogeneous population). Therefore, evolution of the most malignant phenotypes in a tumour cell population is not necessarily consistent tumour growth and invasion since it is modulated by the stromal response. In addition, tumour aggressiveness, as defined by the Gleason score, is differentially modulated by stromal response. These different risk estimations and evolutionary dynamics (and tumour heterogeneity) mean that the overall behaviour of patient tumours is driven by both tumour cells (Gleason score) and the stromal response of the host (ICB).