Advertisement

Research Article Free access | 10.1172/JCI113426

Decay-accelerating factor protects human tumor cells from complement-mediated cytotoxicity in vitro.

N K Cheung, E I Walter, W H Smith-Mensah, W D Ratnoff, M L Tykocinski, and M E Medof

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Cheung, N. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Walter, E. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Smith-Mensah, W. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Ratnoff, W. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Tykocinski, M. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021.

Find articles by Medof, M. in: JCI | PubMed | Google Scholar

Published April 1, 1988 - More info

Published in Volume 81, Issue 4 on April 1, 1988
J Clin Invest. 1988;81(4):1122–1128. https://doi.org/10.1172/JCI113426.
© 1988 The American Society for Clinical Investigation
Published April 1, 1988 - Version history
View PDF
Abstract

The disialoganglioside GD2 is expressed on a wide spectrum of human tumor types, including neuroblastomas and melanomas. Upon binding of 3F8, a murine monoclonal antibody (MAb) specific for GD2, neuroblastomas and some melanomas are sensitive to killing by human complement, whereas some melanomas are not. To investigate the mechanism underlying these differences in complement mediated cytotoxicity, complement-insensitive melanoma cell lines were compared with respect to expression of the decay-accelerating factor (DAF), a membrane regulatory protein that protects blood cells from autologous complement attack. While DAF was undetectable among neuroblastomas, it was present in complement-insensitive melanomas. When the function of DAF was blocked by anti-DAF MAb, C3 uptake and complement-mediated lysis of the insensitive melanoma lines were markedly enhanced. F(ab')2 fragments were as effective in enhancing lysis as intact anti-DAF MAb. The DAF-negative and DAF-positive melanoma cell lines were comparably resistant to passive lysis by cobra venom factor-treated serum. The data suggest that in some tumors, DAF activity accounts for their resistance to complement-mediated killing. The ability to render these cells complement-sensitive by blocking DAF function may have implications for immunotherapy.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (April 1, 1988): No description
Advertisement
Advertisement