Document Detail


Hypoxia increases susceptibility of non-small cell lung cancer cells to complement attack.
MedLine Citation:
PMID:  19259664     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marcin Okroj; Leticia Corrales; Anna Stokowska; Ruben Pio; Anna M Blom
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-04
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  58     ISSN:  1432-0851     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-08-19     Completed Date:  2009-10-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1771-80     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Section of Medical Protein Chemistry, University Hospital, UMAS, Lund University, entrance 46, 205 02 Malmö, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD46 / analysis
Antigens, CD55 / analysis
Antigens, CD59 / analysis
Carcinoma, Non-Small-Cell Lung / immunology,  therapy*
Cell Hypoxia*
Cell Line, Tumor
Cell Survival
Complement Activation
Complement Factor H / genetics
Complement System Proteins / immunology*
Fibrinogen / genetics
Humans
Lung Neoplasms / immunology,  therapy*
Chemical
Reg. No./Substance:
0/Antigens, CD46; 0/Antigens, CD55; 0/Antigens, CD59; 0/CD46 protein, human; 101754-01-2/CD59 protein, human; 80295-65-4/Complement Factor H; 9001-32-5/Fibrinogen; 9007-36-7/Complement System Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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