| Figure 16. Protease activity is
kept in strict equilibrium in healthy cells.
Environmental and endogenous factors can upset this
equilibrium and contribute to the likelihood of a cancer becoming
invasive.
Proteases are maintained in an inactive form, called
proproteases, or even preproproteases. They are made active when other
proteases excise small portions of an inactive protease.
The activity of those proteases is regulated by
certain molecular signals, such as the cytokines secreted by cells of the
immune system.
When protease activity is not required, active
proteases are inhibited by cell-derived molecules, such as
a2-macroglobulin, tissue inhibitor of metalloproteinases (TIMP) and
cystatin. These inhibitors can be destroyed, however, by metabolites such
as hydrogen peroxide and lipid peroxidation products, as well as,
possibly, by some environmental factors.
Proteases and the factors that destroy protease
inhibitors are among the many potential targets for drug interventions
that seek to end metastasis. |
