Melanoma cells constitutively release an anchor-positive soluble form of protectin (sCD59) that retains functional activities in homologous complement-mediated cytotoxicity.

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Abstract
Protectin (CD59), a glycosylphosphatidylinositol-anchored cell membrane glycoprotein, is differentially expressed on melanocytic cells and represents the main restriction factor of C-mediated lysis of melanoma cells. In this study, we re- port that CD59-positive melanoma cells constitutively re- lease a soluble form of CD59 (sCD59), and that its levels di- rectly correlate ( r 5 0.926; P , 0.05) with the amount of membrane-bound CD59. SDS-PAGE analysis showed that the molecular components of sCD59 are similar to those of cellular CD59 expressed by melanoma cells. Melanoma- released sCD59 is anchor positive since it inserts into cell membranes of homologous cells that transiently increase their expression of CD59. Moreover, sCD59 is functional: it blocks the binding of the anti-CD59 mAb YTH53.1 to mela- noma cells and reverses its effects on C-mediated lysis. In fact, preincubation of mAb YTH53.1 with scalar doses of conditioned media of CD59-positive but not of CD59-nega- tive melanoma cells reduced significantly ( P , 0.05), and in a dose-dependent fashion, the enhancement of C-mediated lysis of anti-GD3-sensitized melanoma cells induced by the masking of cellular CD59 by mAb YTH53.1. Altogether, these data demonstrate that CD59-positive human mela- noma cells release a soluble form of CD59 that is structur- ally similar to cellular CD59, retains its anchoring ability, is functional, and may impair the effectiveness of clinical ap- proaches to humoral immunotherapy for human mela- noma. ( J. Clin. Invest. 1997. 100:1248-1255.) Key words: GPI anchorPI-PLCsheddingimmunotherapymalig- nant disease