Complement resistance of tumor cells: Basal and induced mechanisms

K. Jurianz, S. Ziegler, H. Garcia-Schüler, S. Kraus, O. Bohana-Kashtan, Z. Fishelson, M. Kirschfink

Research output: Contribution to journalArticlepeer-review

Abstract

Clinical and experimental studies have suggested that complement may play a role in tumor cytotoxicity. However, the efficiency of complement- mediated tumor cell lysis is hampered by various protective mechanisms, which may be divided into two categories: basal and induced mechanisms. The basal mechanisms are spontaneously expressed in cells without a need for prior activation, whereas the induced mechanisms develop in cells subjected to stimulation with cytokines, hormones, drugs or with sublytic doses of complement and other pore-formers. Membrane-associated complement regulatory proteins, such as CD55 (DAF, Decay-Accelerating Factor), CD46 (MCP, Membrane Cofactor Protein), CD35 (CR1, Complement Receptor type 1) and CD59, which serve as an important mechanism of self protection and render autologous cells insensitive to the action of complement, appear to be over-expressed on certain tumors. Furthermore, tumor cells secrete several soluble complement inhibitors. Tumor cells may also express proteases that degrade complement proteins, such as C3, or ecto-protein kinases which can phosphorylate complement components, such as C9. Besides this basal resistance, nucleated cells resist, to some extent, complement damage by removing the membrane attack complexes (MAC) from their surface. Several biochemical pathways, including protein phosphorylation, activation of G-proteins and turnover of phosphoinositides have been implicated in resistance to complement. Calcium ion influx and activation of protein kinase C (PKC) and of mitogen-activated protein kinase (MAPK) have also been demonstrated to be associated with the complement-induced enhanced resistance to lysis. The complete elucidation of the molecular mechanisms involved in basal and induced tumor cell resistance will enable the development of strategies for interfering with these evasion mechanisms and the use of the cytotoxic complement system against tumor cells. (C) 1999 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)929-939
Number of pages11
JournalMolecular Immunology
Volume36
Issue number13-14
DOIs
StatePublished - Sep 1999

Keywords

  • Complement
  • Regulation
  • Resistance mechanisms
  • Tumor

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