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Hypoxia increases susceptibility of non-small cell lung cancer cells to complement attack.

Okroj, Marcin LU ; Corrales, Leticia; Stokowska, Anna; Pio, Ruben and Blom, Anna LU (2009) In Cancer immunology, immunotherapy : CII 58. p.1773-1782
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer immunology, immunotherapy : CII
volume
58
pages
1773 - 1782
publisher
Springer
external identifiers
  • wos:000269112900005
  • pmid:19259664
  • scopus:70349786130
ISSN
1432-0851
DOI
10.1007/s00262-009-0685-8
language
English
LU publication?
yes
id
7e61d221-b12d-47fe-a4e6-ca2f542db615 (old id 1368026)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19259664?dopt=Abstract
date added to LUP
2009-04-03 13:00:10
date last changed
2017-01-15 04:26:49
@article{7e61d221-b12d-47fe-a4e6-ca2f542db615,
  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.},
  author       = {Okroj, Marcin and Corrales, Leticia and Stokowska, Anna and Pio, Ruben and Blom, Anna},
  issn         = {1432-0851},
  language     = {eng},
  pages        = {1773--1782},
  publisher    = {Springer},
  series       = {Cancer immunology, immunotherapy : CII},
  title        = {Hypoxia increases susceptibility of non-small cell lung cancer cells to complement attack.},
  url          = {http://dx.doi.org/10.1007/s00262-009-0685-8},
  volume       = {58},
  year         = {2009},
}