ArticleClinical and experimental immunology2003
Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid.
Article in Clinical and experimental immunology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 136 citations in OpenAlex.
- Reducing sialylation in melanoma increases classical pathway-mediated complement activation.iScience · 2026Article
- Complement system in tumor growth and metastases.British journal of cancer · 2026Review
- Chemotherapy of breast cancer cells alters susceptibility to complement-mediated opsonization and killing.Medical oncology (Northwood, London, England) · 2025Article
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- RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review.International journal of molecular sciences · 2022Review
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- Development and Characterization of an Anti-Cancer Monoclonal Antibody for Treatment of Human Carcinomas.Cancers · 2022Review
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- How Structures of Complement Complexes Guide Therapeutic Design.Sub-cellular biochemistry · 2021Review
- The Current Landscape of Antibody-based Therapies in Solid Malignancies.Theranostics · 2021Review
- The Neutrophil: The Underdog That Packs a Punch in the Fight against Cancer.International journal of molecular sciences · 2020Review
- Drivers and regulators of humoral innate immune responses to infection and cancer.Molecular immunology · 2020Review
- Complement System: a Neglected Pathway in Immunotherapy.Clinical reviews in allergy & immunology · 2020Review
- B cells in transplant tolerance and rejection: friends or foes?Transplant international : official journal of the European Society for Organ Transplantation · 2020Review
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- Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention.Frontiers in immunology · 2019Review
- The Role of Membrane Bound Complement Regulatory Proteins in Tumor Development and Cancer Immunotherapy.Frontiers in immunology · 2019Review
- Role of C5b-9 and RGC-32 in Cancer.Frontiers in immunology · 2019Review
- Article
- Cooperation between Hsp90 and mortalin/GRP75 in resistance to cell death induced by complement C5b-9.Cell death & disease · 2018Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleated cells employ several strategies to evade killing by homologous complement. We studied complement resistance in the human carcinoma cell lines (CA) T47D (mammary), SKOV3 (ovarian), and PC-3 (prostate) with emphasis on the following mechanisms of defense: 1. Expression and shedding of the membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59; 2. Resistance based on protein phosphorylation; 3. Cell surface expression of sialic acid residues; 4. Desensitization to complement upon exposure to sublytic complement doses. Anti-mCRP antibody blocking experiments demonstrated that CD59 is the main mCRP protecting these CA from complement. Soluble CD59 was also found in supernates of PC-3> SKOV3 > T47D cells. Second, inhibitors of PKC, PKA and MEK sensitized the CA to lysis, thus implicating these protein kinases in CA complement resistance. Third, removal of sialic acid residues with neuraminidase also sensitized CA to lysis. Finally, exposure of CA to sublytic doses of complement conferred on them enhanced resistance to lytic complement doses in a PKC-dependent process. Combined treatment of CA with anti-CD59 antibodies, PD98059 (a MEK inhibitor) and neuraminidase produced a large enhancement in CA sensitivity to complement. Our results show that CD59 and sialic acid residues present on the cell surface, and intracellular processes involving protein phosphorylation act additively to secure CA resistance to complement-mediated lysis. Therefore, the effectiveness of antibody- and complement-based cancer immunotherapy will markedly improve by suppression of the various complement resistance mechanisms.
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