Figure 3.

Flowcharts with the life cycle of the different cell phenotypes. (a) Tumour cells produce TGF-β (which they need for proliferation) and MDEs. They proliferate when there is enough TGF-β and have reached maturity. An insufficient local concentration of TGF-β triggers cell death. (b) Basal cells replace missing luminal cells and produce TGF-β to suppress proliferation. (c) Normal luminal cells consume TGF-β and die when they are surrounded by tumour cells. (d) Non motile stroma cells consume TGF-β but will produce more when the local concentration exceeds threshold. (e) Motile stromal cells are constantly moving chemotactically towards the direction of the TGF-β gradient. (f) Key interactions between the cell types and biologically active substances. Solid lines denote reduction in concentration by consumption, killing, or inhibition of production at the end with the small red cross bar. Dashed lines denote increases in concentration by promotion of production or proliferation at the end(s) with the arrow and (+) symbol. The double arrow between tumour cells and TGF-β represents TGF-β production by the tumour cells that in turn results in tumour cell proliferation by TGF-β.