Procathepsin-L, a proteinase that cleaves human C3 (the third component of complement), confers high tumorigenic and metastatic properties to human melanoma cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 1998-07, Vol.58 (13), p.2733-2736
• Main Authors: FRADE, R, RODRIGUES-LIMA, F, SUYUN HUANG, KEPING XIE, GUILLAUME, N, BAR-ELI, M
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cathepsin L; Cathepsins - genetics; Cathepsins - metabolism; Cathepsins - physiology; Complement C3 - immunology; Dermatology; Enzyme Precursors - genetics; Enzyme Precursors - metabolism; Enzyme Precursors - physiology; Humans; Medical sciences; Melanoma - enzymology; Melanoma - immunology; Melanoma - secondary; Mice; Mice, Inbred BALB C; Mice, Nude; Phenotype; Skin Neoplasms - enzymology; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Transfection; Tumor Cells, Cultured; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0008-5472; 1538-7445

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.