It is likely that different MMPs are involved at specific stages during which cancer cells become metastatic. Determining the levels of active MMPs in tissue could provide crucial information about the mechanisms of regulation of MMP activity. Two other protease families are also under investigation for activity during metastasis. It is possible that members of some or all of these families of proteases interact during metastasis. The secretion of proteases, such as cathepsin-B, by cancer cells demonstrates another way these cells deviate from normal.
Lysosomes are the cellular trash cans that do double-duty as recycling centers.
Bonnie Sloane and her colleagues at Wayne State University School of Medicine in Detroit have discovered that cathepsin-B can be found in the extracellular environment of invading cancer cells. Furthermore, it appears that the invading cells not only secrete cathepsin-B, but can subsequently bind it to their surfaces. Once the metastasis is established at its new site, cathepsin-B continues to be expressed on the membrane, but in an inactive form. Such observations suggest that these proteases are at the head of a cascade of proteases that ultimately activate MMPs, which in turn chew up proteins of the connective matrix. Figure 9 Metastasis is therefore a complex process, requiring the cancer cells first to release themselves of their intercellular adhesive bonds, then leave their cellular microenvironment and migrate through the connective tissue matrix encapsulating their tissue compartment in order to gain access to the blood vessels that carry them to a new organ.