Human C3 is a multipotent molecule which participates to different events involved in immune response as complement activation, antigen presentation, cell-cell interactions and cell proliferation. Thus,
proteinases which cleave C3 may modify C3-dependent cellular functions. This led us to identify two membrane-associated
proteinases which cleave human C3: (a) A
p57 serine proteinase expressed on human erythrocyte membranes--This p57
proteinase shared
antigenic determinants with ankyrine and may be involved in clearance of
immune complexes; (b) A p41
cysteine proteinase, which shares
antigenic determinants, amino-acid sequence and specific activity with
procathepsin-L--This p41 C3-cleaving cyteine
proteinase is also involved in tumorigenic and metastatic properties of human
melanoma in nude mice. Indeed, pretreatment of highly tumorigenic and metastatic
melanoma cells with anti-p39 Ab totally abolished their tumorigenicity and significantly decreased the number of experimental lung
metastases in nude mice. Furthermore, overexpression of
procathepsin-L in nonmetastatic
melanoma cells increased their tumorigenicity and switched their phenotype to highly metastatic cells in nude mice. Altogether, these data support that expression and secretion of
procathepsin-L, which cleaves human C3, might be one of the multiple mechanisms by which
tumor cells escape the immune surveillance.