Figure 2. Summary of stromal conditions, species, and cells affecting and affected by cancer cell activity.

Within the tumour stroma, environmental conditions, mechanical forces and extracellular matrix (ECM) structure, stromal cell activity, and the activity of various extracellular signalling molecules and enzymes all affect and are affected by cancer cell activity. Environmental conditions like pH and microenvironmental oxygen content affect cancer cell metabolism, but are also heavily influenced by cancer cell activity. Cancer cells also mechanically interact with the surrounding ECM and modulate their behaviour according to ECM mechanical properties such as stiffness and fibre architecture, but also respond to dynamic stimuli such as mechanical forces conducted through the ECM and interstitial flows and pressures. Furthermore, the integrins through which the cancer cells form focal adhesions with the ECM structure can initiate signalling pathways within the cancer cells in addition to conduction mechanical forces. The activity of stromal cells, such as the fibroblast pictured above, are heavily affected by cancer paracrine signalling in the tumour microenvironment, but also can change the physical and signalling characteristics of the microenvironment, both of which are significant determinants of cancer cell behaviour. The activity of signalling molecules, such as the pictured cytokines but also growth and survival factors, within the tumour microenvironment are also important determinants of not only cancer cell behaviour but also of stromal and immune cell (not pictured) behaviour. Finally, enzymatic activity, such as that of matrix metalloproteinases (MMPs), can shape the tumour microenvironment both physically and chemically, both of which can greatly affect cancer cell behaviour.