Mast cell chymase is in contact with melanoma cells in vivo and it detaches melanoma cells from the substratum in vitro.

Abstract

Mast cell chymase, a chymotryptic serine proteinase, is a powerful enzyme that may liberate adherent tumor cells thereby promoting tumor spread. This study investigated interactions between cells containing immunoreactive chymase and melanoma cells in 101 melanoma and 50 nevus specimens as well as used recombinant human (rh)-chymase and WM115 and G361 primary melanoma cell lines in culture. Rh-chymase at low concentration (0.1 µg/mL) detached both melanoma cell lines from noncoated or collagen-coated plastic surface, but this effect was regulated by heparin and heparinase. After prolonged treatment at high rh-chymase (1-5 µg/mL) the growth pattern of detached and re-seeded cells was abnormal. Decreased migration and proliferation at up to 0.005-0.01 µg/mL rh-chymase was noticed in WM115 cells, while rh-chymase at 1-5 µg/mL partially reduced the viability of G361 cells. Of importance is the finding that melanoma cell lines are not uniform as there was variation between cell lines with regard to the concentration of rh-chymase needed for these effects. Sonicates prepared from the cell lysates did not inhibit the enzymatic activity of rh-chymase. The interactions were confirmed morphologically by detecting apparent contacts between chymase+ cells and melanoma cells in melanoma specimens. These results suggest that chymase can detach melanoma cells from the tumor, but this effect is regulated by heparin, and their proliferation, migration or viability can be reduced by chymase. Thus, the effect of chymase may be antitumorigenic, rather than protumorigenic.