Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors
Okroj, Marcin LU ; Hsu, Yi-Fan ; Ajona, Daniel ; Pio, Ruben and Blom, Anna LU
(2008)
In Molecular Immunology
45(1).
p.169-179
- Abstract
- 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.... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1143967
- author
- Okroj, Marcin
LU
; Hsu, Yi-Fan
; Ajona, Daniel
; Pio, Ruben
and Blom, Anna
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Complement, Tumor, NSCLC, Immune system, Cytotoxicity
- in
- Molecular Immunology
- volume
- 45
- issue
- 1
- pages
- 169 - 179
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- pmid:17548110
- wos:000250013600019
- scopus:34548288545
- pmid:17548110
- ISSN
- 1872-9142
- DOI
- 10.1016/j.molimm.2007.04.025
- language
- English
- LU publication?
- yes
- id
- 441afa98-452b-4b57-b6d0-4f6b2d613c19 (old id 1143967)
- date added to LUP
- 2016-04-01 12:57:39
- date last changed
- 2022-01-27 08:34:48
@article{441afa98-452b-4b57-b6d0-4f6b2d613c19,
abstract = {{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.}},
author = {{Okroj, Marcin and Hsu, Yi-Fan and Ajona, Daniel and Pio, Ruben and Blom, Anna}},
issn = {{1872-9142}},
keywords = {{Complement; Tumor; NSCLC; Immune system; Cytotoxicity}},
language = {{eng}},
number = {{1}},
pages = {{169--179}},
publisher = {{Pergamon Press Ltd.}},
series = {{Molecular Immunology}},
title = {{Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors}},
url = {{http://dx.doi.org/10.1016/j.molimm.2007.04.025}},
doi = {{10.1016/j.molimm.2007.04.025}},
volume = {{45}},
year = {{2008}},
}