ArticleCancer immunology, immunotherapy : CII2009
Hypoxia increases susceptibility of non-small cell lung cancer cells to complement attack.
Article in Cancer immunology, immunotherapy : CII, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Hypoxia-induced complement component 3 promotes aggressive tumor growth in the glioblastoma microenvironment.JCI insight · 2024Article
- The Factor H protein family: The switchers of the complement alternative pathway.Immunological reviews · 2023Review
- Review
- Association of Complement-Related Proteins in Subjects With and Without Second Trimester Gestational Diabetes.Frontiers in endocrinology · 2021Article
- Complement and Cancer-A Dysfunctional Relationship?Antibodies (Basel, Switzerland) · 2020Review
- Drivers and regulators of humoral innate immune responses to infection and cancer.Molecular immunology · 2020Review
- Context-dependent roles of complement in cancer.Nature reviews. Cancer · 2019Review
- Complement in Metastasis: A Comp in the Camp.Frontiers in immunology · 2019Review
- The tumour microenvironment links complement system dysregulation and hypoxic signalling.The British journal of radiology · 2019Review
- Mutations in an Innate Immunity Pathway Are Associated with Poor Overall Survival Outcomes and Hypoxic Signaling in Cancer.Cell reports · 2018Article
- The complement system in the airway epithelium: An overlooked host defense mechanism and therapeutic target?The Journal of allergy and clinical immunology · 2018Review
- Complement Activation as a Helping Hand for Inflammophilic Pathogens and Cancer.Frontiers in immunology · 2018Review
- Differences in the Plasma Proteome of Patients with Hypothyroidism before and after Thyroid Hormone Replacement: A Proteomic Analysis.International journal of molecular sciences · 2018Article
- The dual role of complement in cancer and its implication in anti-tumor therapy.Annals of translational medicine · 2016Review
- Article
- Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.Cancer immunology, immunotherapy : CII · 2015Article
- The alternative complement pathway regulates pathological angiogenesis in the retina.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- The role of complement in tumor growth.Advances in experimental medicine and biology · 2014Review
- Investigation of complement activation product c4d as a diagnostic and prognostic biomarker for lung cancer.Journal of the National Cancer Institute · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement system can be specifically targeted to tumor cells due to molecular changes on their surfaces that are recognized by complement directly or via naturally occurring antibodies. However, tumor cells often overexpress membrane-bound complement inhibitors protecting them from complement attack. We have previously shown that non-small cell lung cancer (NSCLC) cells, additionally to membrane-bound inhibitors, produce substantial amounts of soluble regulators such as factor I (FI) and factor H (FH). Since low oxygen concentration is associated with rapidly growing solid tumors, we studied how NSCLC cells protect themselves from complement attack under hypoxic conditions. Unexpectedly, mRNA levels and secretion of both FI and FH were significantly decreased already after 24 h exposure to hypoxia while cell viability measured by XTT assay and annexin V/7-AAD staining was affected only marginally. Furthermore, we observed decrease of mRNA level and loss of membrane-bound complement inhibitor CD46 and increased deposition of early (C3b) and terminal (C9) complement components on hypoxic NSCLC cells. All three complement pathways (classical, lectin and alternative) were employed to deposit C3b on cell surface. Taken together, our results imply that under hypoxic conditions NSCLC give up some of their available defense mechanisms and become more prone to complement attack.
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