We have used an extract of basement membranes which can be reconstituted into a biologically active gel matrix composed predominantly of
collagen IV,
laminin,
nidogen, and
heparin sulfate proteoglycan, in order to study the mechanisms involved in
tumor cell invasion. When layered onto a porous filter in a Boyden chamber, the gel forms a barrier to the passage of normal cells. Malignant cells are able to cross this layer when the
conditioned medium of NIH 3T3 cells is used as a
chemoattractant to stimulate cell migration. A variety of human
tumor cells have thus been studied in this system and we find a high correlation between their invasiveness in vitro and their malignant behavior as exhibited in vivo. We have used this in vitro invasion assay to test for factors which might inhibit
tumor cell invasion.
Collagenase IV is produced by malignant cells and is thought to be required for invasion. Indeed, inhibitors of this
enzyme have demonstrated reduced
tumor cell invasiveness. One site of five
amino acids, on the B1 chain, which has been shown to promote cell adhesion, migration and binding to
laminin receptor, was found to inhibit the invasion of
tumor cells. In addition, factors which elevated cAMP levels were also able to suppress the invasiveness of
tumor cells. These data suggest that the assay system described herein can be successfully utilized to study the invasive activity of
tumor cells and those factors that may inhibit the spread of malignant cells.