Inhibition of plasminogen activators and the growth of cultured human tumour cells

Changes in sensitivity of human tumour cells to growth inhibition by proteinase inhibitors.

“…The conversioncorrelated with the cell-surfaceproteinase activity becoming resistant to the inhibitory action of alAT. This situation is markedly different from that in other resistant tumour cell lines, such as HT 1080, HeLa and MM96, in which the cell-surface proteinase activity is still inhibited by anti-GRP antibodies or by alAT (Pitts and Scott, 1983;Scott, 1988; see also below). At this stage, we can offer no explanation as to why this change in the susceptibility of the enzyme to the inhibitor occurs, but it is noteworthy that all cells previously tested appear to have a sterically-inaccessible fraction of their cell-surface proteinase, at least to macromolecular inhibitors (Scott et al ., 1989) .…”

“…GRP activity was always present, but GRP inhibition led to growth inhibition in only six "sensitive" types. Ten culture types, mostly established tumour cell lines, were resistant to GRP inhibitors; in most of these cases, GRP inhibition was observed, but the cells continued to grow (Pitts and Scott, 1983;Scott, 1988;Scott and Tse, 1992). Because in one case, there was some evidence for a change from the sensitive to the resistant state during the course of maintenance of the cell strain in culture, it was hypothesised that the change could be part of the phenomenon of tumour progression (Pitts and Scott, 1983).…”

Inhibition of an endogenous growth‐related proteinase enhances the recovery of a negative growth regulator from cultured human cells.

“…Human fibroblasts (strain MPS) and the human epidermal carcinoma cell line HELA were maintained and cultured as previously described (Scott and Seow, 1985;Scott, 1988), as were human U2-0S osteosarcoma cells and bovine corneal endothelial cells (Scott and Tse, 1992). To collect endogenous Bgalactoside-binding proteins from MPS fibroblasts, newly-confluent cultures were washed with serum-free Dulbecco's modified Eagle's medium and then incubated in minimal volumes (10 ml in a 75 cnr' culture flask) for up to 7 days.…”

“…Vol. 17, No.3, 1993 (Pitts and Scott, 1983;Scott, 1988;Scott and Tse, 1992).Further work in this area is clearly desirable.…”

“…One enzyme, the so-called growth-related proteinase (GRP), was first isolated from human leukocyte membranes as a serine proteinase with a molecular weight of about 75,000. Antibodies to this enzyme inhibited the growth of many human cell types in culture, as did specific macromolecular proteinase inhibitors (Allen et ai, 1981;Pitts and Scott, 1983;Scott and Seow, 1985;Scott, 1988). Antibody affinity chromatography was used to identify similar enzymes in a range of cells and body fluids (Harper et ai, 1984).…”