Collagenase effects on cancer cell invasiveness and motility

The invasion by malignant cells through extracellular matrix is an important part of the metastatic process, providing access to points of dissemination. Cell migration in tissues, however, depends not only on the destruction of extracellular matrices, but also on the locomotory behavior of the cells themselves. A quantitative study of aspects of cell behavior related to invasiveness was made using cellulose nitrate filters, both unimpregnated and filled with collagen, as models for some aspects of basement membrane. The relative penetration of mouse malignant cells into filters correlated with their spontaneous metastatic potential. Penetration of collagen-impregnated filters was greater than in unfilled filters. Pretreatment with collagenase enhanced the penetration of some cells into both collagen-impregnated and unfilled filters, and enhanced their motility on a plastic substrate; other cells showed enhanced penetration when incubated on collagenase-pretreated filters and no change in motility on the plastic substrate when incubated in collagenase-containing medium. These results emphasize the variability in response of different malignant cell types to factors present in the tumor environment and suggest that the effect of collagenase during invasion may be to enhance cell motility as well as to degrade the extracellular matrix.