Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression

Abstract

Tumors are like new organs and are made of multiple cell types and components. The tumor competes with the normal microenvironment to overcome antitumorigenic pressures. Before that battle is won, the tumor may exist within the organ unnoticed by the host, referred to as 'occult cancer'. We review how normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state. We also include a discussion of how this information is being tailored for clinical use.

Figure 1

The normal tissue microenvironment acts as a barrier to tumorigenesis. Under conditions of normal tissue homeostasis, the microenvironment exerts suppressive forces to keep occult tumors in check (bottom left in graph). But the microenvironment can also be permissive to tumor growth, and the combination of mutagens, inflammation, growth factors and other tissue-associated promotional forces can breach the barrier to tumor formation, resulting in full-blown cancer (top right).