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Procathepsin-L, a Proteinase that Cleaves Human C3 (the Third Component of Complement), Confers High Tumorigenic and Metastatic Properties to Human Melanoma Cells¹

Immunochimie des Régulations Cellulaires et des Interactions Virales, Centre INSERM, Hôpital Saint-Antoine, 75012, Paris, France [R. F., F. R-L., N. G.]; and Department of Cell Biology, U. T. M. D. Anderson Cancer Center, Houston, Texas 77030 [S. H., K. X., M. B-E.]

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.

¹ Supported by Institut National de la Santé et de la Recherche Medicale (INSERM), Comité de Paris de la Ligue Nationale Francaise contre le Cancer (to R. F.) and in part by NIH Grant CA-64137 (to M. B-E.). R. F. and M. B-E. are recipients of Nato Grant CRG.960566.

² To whom requests for reprints should be addressed, at INSERM U.354, Centre INSERM, Hôpital Saint-Antoine, 75012, Paris, France.

Received 4/ 1/98. Accepted 5/15/98.

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