Overexpression of protectin (CD59) down-modulates the susceptibility of human melanoma cells to homologous complement

Sandra Coral, Ester Fonsatti, Luca Sigalotti, Chiara De Nardo, Alberto Visintin, Gianpaolo Nardi, Francesca Colizzi, Mario P. Colombo, Gaetano Romano, Maresa Altomonte, Michele Maio

Research output: Contribution to journalArticlepeer-review

Abstract

The clinical efficacy of therapeutic complement (C)-activating monoclonal antibodies (mAb) to melanoma-associated antigens can be impaired by the levels of expression of C-inhibitory molecules on neoplastic cells. Protectin (CD59) is a glycosylphosphatidylinositol (GPI)-anchored cell membrane glycoprotein, acting as terminal regulator of C cascade, which is heterogeneously expressed in melanomas and represents the main restriction factor of C-mediated lysis of melanoma cells. Thus, we investigated whether the overexpression of CD59 could influence the constitutive susceptibility of distinct melanoma cells to homologous C. Infection of CD59-positive Mel 100 and 70-W melanoma cells by a retroviral vector carrying the CD59 cDNA, significantly (P <0.05) upregulated their constitutive expression of CD59, whereas it did not affect that of additional C-regulatory molecules. Transduced CD59 was entirely GPI-anchored and showed a molecular weight identical to native CD59. Additionally, higher amounts of soluble CD59 were detected in the conditioned media of CD59-transduced melanoma cells compared with parental cells. CD59-transduced melanoma cells, sensitized by the anti-GD3 disialoganglioside mAb R24, were significantly (P <0.05) less susceptible to homologous C-lysis than were parental cells; this effect was fully reverted by the masking of CD59 with F(ab')2 fragments of the anti-CD59 mAb YTH53.1. These results provide conclusive evidence demonstrating that absolute levels of CD59 expression regulate the susceptibility to homologous C of specific melanoma cells, and suggest an additional explanation for the poor clinical results obtained with C-activating mAb in the clinical setting. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalJournal of Cellular Physiology
Volume185
Issue number3
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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