Quantitation of basement membrane collagen degradation by living tumor cells in vitro.

In order to study the mechanism of tumor cell invasion of basement membranes, a new method has been developed to quantify basement membrane (type IV) collagen degradation by living tumor cells. Tumor cells are inoculated into 16-mm tissue culture wells coatd with biosynthetically [14C]proline-labeled type IV collagen. Soluble degradation products are detected by measuring the radioactivity present in the medium. Using this method, we find that both highly metastatic and non-metastatic tumor cells and normal cells attach, but only the metastatic cells degrade the type IV collagen layer. The present data suggest that the mechanism of degradation is local activation of a latent type IV collagen specific enzyme at the cell substrate interface with no significant cell phagocytosis of substrate.