Abstract
Various types of proteinases are implicated in the malignant
progression of human and animal tumors.
Proteinase inhibitors may therefore be useful as therapeutic
agents in antiinvasive and antimetastatic
treatment. The aims of this study were (1) to estimate
the relative importance of proteinases in B16 cell invasion
in vitro using synthetic, classspecific proteinase
inhibitors and (2) to assess the inhibitory effect
of some naturally occurring cysteine proteinase
inhibitors. Serine proteinase inhibitor reduced invasiveness
by up to 24%, whereas inhibition of aspartic
proteinases reduced invasion by 11%. Synthetic inhibitors
of cysteine proteinases markedly impaired
invasion: cathepsin B inhibitors, particularly Ca
074Me, inhibited invasion from 20 40%, whereas
cathepsin L inhibitor Clik 148 reduced invasion by
11%. The potato cysteine proteinase inhibitor PCPI
8.7 inhibited invasion by 21%, whereas another potato
inhibitor, PCPI 6.6, and the mushroom cysteine
proteinase inhibitor clitocypin had no effects. As the
inhibitors that inhibited cathepsin B were in general
more efficient at impairing the invasiveness, we conclude
that of the two cysteine proteinases, cathepsin
B plays a more important role than cathepsin L in
murine melanoma cell invasion.