PROCATHEPSIN-L, A PROTEINASE THAT CLEAVES HUMAN C3 (THE 3RD COMPONENTOF COMPLEMENT), CONFERS HIGH TUMORIGENIC AND METASTATIC PROPERTIES TOHUMAN-MELANOMA CELLS

We previously demonstrated that highly metastatic human melanoma cells secrete a 41 kDa proteinase that cleaves C3, the third component of c omplement, and shares antigenic determinants with procathepsin-l. Thus , we herein transfected the nonmetastatic DX-3 melanoma cells with the procathepsin-l cDNA, Three clones expressing and secreting high level s of procathepsin-l were selected. Conditioned medium and whole cell e xtracts from these clones, but not from control cells, carried a high C3-cleaving activity. The transfected clones displayed up to 60% resis tance to complement-mediated lysis, Overexpression of procathepsin-l i n melanoma cells increased their tumorigenicity and switched their phe notype from nonmetastatic to highly metastatic cells. This is the firs t report that demonstrates that enforced expression of procathepsin-l by human melanoma cells arms them with the ability to inactivate compl ement-mediated lysis and contributes to tumor growth and metastasis.