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

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.
AuthorsS Coral, E Fonsatti, L Sigalotti, C De Nardo, A Visintin, G Nardi, F Colizzi, M P Colombo, G Romano, M Altomonte, M Maio
JournalJournal of cellular physiology (J Cell Physiol) Vol. 185 Issue 3 Pg. 317-23 (Dec 2000) ISSN: 0021-9541 [Print] UNITED STATES
PMID11056001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2000 Wiley-Liss, Inc.
Chemical References
  • Antigens, CD59
  • Antigens, CD59 (biosynthesis, genetics)
  • Complement Activation (genetics)
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic (immunology)
  • Genetic Vectors
  • Humans
  • Melanoma (genetics, immunology)
  • Retroviridae
  • Transfection
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: