Procathepsin-L, a proteinase that cleaves human C3 (the third component of complement), confers high tumorigenic and metastatic properties to human melanoma cells.
We previously demonstrated that highly metastatic human melanoma cells secrete a 41 kDa proteinase that cleaves C3, the third component of complement, 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 levels of procathepsin-L were selected. Conditioned medium and whole cell extracts from these clones, but not from control cells, carried a high C3-cleaving activity. The transfected clones displayed up to 60% resistance to complement-mediated lysis. Overexpression of procathepsin-L in melanoma cells increased their tumorigenicity and switched their phenotype from nonmetastatic to highly metastatic cells. This is the first report that demonstrates that enforced expression of procathepsin-L by human melanoma cells arms them with the ability to inactivate complement-mediated lysis and contributes to tumor growth and metastasis.
Frade
R
R
Immunochimie des Régulations Cellulaires et des Interactions Virales, Centre INSERM, Hôpital Saint-Antoine, Paris, France.
Rodrigues-Lima
F
F
Huang
S
S
Xie
K
K
Guillaume
N
N
Bar-Eli
M
M
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003176:Complement C3 / Q000276:immunology; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000276:immunology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D012878:Skin Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D003176:Complement C3; D004792:Enzyme Precursors; D002403:Cathepsins; C063905:procathepsin L; D056668:Cathepsin L