Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors
Author
Summary, in English
The complement system is important for protection from invading pathogens, removal of waste products and guidance of the immune response. Furthermore, complement can be also targeted to cancer cells. However, membrane-bound inhibitors over-expressed by certain types of tumor cells restrict the cytotoxic activity of complement. Herein we report that non-small cell lung cancer (NSCLC) cells produce soluble complement inhibitors factor I (FI) and C4b-binding protein (C4BP). FI is a serine protease capable of degrading the activated complement components C3b and C4b, whilst C4BP acts as its cofactor. Furthermore, NSCLC cells express membrane-bound regulators and shed membrane cofactor protein (MCP), which shares cofactor function with C4BP. Secretion of FI from NSCLC cells was higher than previously reported for any non-hepatic source and FI produced by these cells could efficiently support cleavage of C3b and C4b. In vitro functional assays revealed that additional FI significantly decreased C3 deposition and complement-dependent lysis, particularly when cofactors were added. Our results demonstrate that soluble inhibitors produced by NSCLC cells may provide further protection from complement beyond the level ensured by membrane-bound inhibitors and, as such, contribute to the aggressive phenotype of these lung cancer cells.
Department/s
Publishing year
2008
Language
English
Pages
169-179
Publication/Series
Molecular Immunology
Volume
45
Issue
1
Document type
Journal article
Publisher
Pergamon Press Ltd.
Topic
- Immunology in the medical area
Keywords
- Complement
- Tumor
- NSCLC
- Immune system
- Cytotoxicity
Status
Published
Research group
- Protein Chemistry, Malmö
ISBN/ISSN/Other
- ISSN: 1872-9142