A cysteine proteinase, which cleaves human C3, the third component of complement, is involved in tumorigenicity and metastasis of human melanoma.
The DM-4 human melanoma cell line, which is highly metastatic in nude mice, expresses a C3-cleaving activity that proteolyzes labeled as well as unlabeled human C3. This C3-cleaving activity is a cysteine proteinase characterized by a M(r) 41,000. The p41 proteinase shares antigenic determinants with murine p39 procathepsin-L and human procathepsin-L. Preincubation of DM-4 cells with anti-p39 F(ab')2 induced up to 45% decrease in their complement resistance. Pretreatment of DM-4 cells with anti-p39 Ab strongly inhibited their tumorigenicity and significantly decreased their metastatic potential in nude mice. Thus, the p41 C3-cleaving proteinase contributes to tumorigenicity and metastasis of human melanoma DM-4 cells.
Jean
D
D
Immunochimie des Régulations Cellulaires et des Interactions Virales, INSERM U.354, Centre INSERM, Hôpital Saint-Antoine, Paris, France.
Bar-Eli
M
M
Huang
S
S
Xie
K
K
Rodrigues-Lima
F
F
Hermann
J
J
Frade
R
R
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D010450:Endopeptidases; D000939:Epitopes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D003176:Complement C3; D000939:Epitopes; D009363:Neoplasm Proteins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse