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Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.

Okroj, Marcin LU ; Holmquist, Emelie LU ; Nilsson, Elise LU ; Anagnostaki, Lola; Jirström, Karin LU and Blom, Anna LU (2015) In Cancer Immunology and Immunotherapy 64(4). p.467-478
Abstract
Tumor cells often evade killing by the complement system by overexpressing membrane-bound complement inhibitors. However, production of soluble complement inhibitors in cells other than hepatocytes was rarely reported. We screened several breast cancer cell lines for expression of soluble complement inhibitor, complement factor I (FI). We also analyzed local production of FI in tissue microarrays with tumors from 130 breast cancer patients by in situ hybridization and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA and protein levels was also confirmed in tumor cells and tumor stroma, both in fibroblasts and infiltrating immune... (More)
Tumor cells often evade killing by the complement system by overexpressing membrane-bound complement inhibitors. However, production of soluble complement inhibitors in cells other than hepatocytes was rarely reported. We screened several breast cancer cell lines for expression of soluble complement inhibitor, complement factor I (FI). We also analyzed local production of FI in tissue microarrays with tumors from 130 breast cancer patients by in situ hybridization and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA and protein levels was also confirmed in tumor cells and tumor stroma, both in fibroblasts and infiltrating immune cells. Multivariate Cox regression analyses revealed that high expression of FI protein in tumor cells was correlated with significantly shorter cancer-specific survival (HR 2.8; 95 % CI 1.0-7.5; p = 0.048) and recurrence-free survival (HR 3.4; 95 % CI 1.5-7.4; p = 0.002). High FI expression was positively correlated with tumor size (p < 0.001), and Nottingham histological grade (p = 0.015) and associated with estrogen and progesterone receptor status (p = 0.03 and p = 0.009, respectively). Our data show that FI is expressed in breast cancer and is associated with unfavorable clinical outcome. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Immunology and Immunotherapy
volume
64
issue
4
pages
467 - 478
publisher
Springer
external identifiers
  • pmid:25618258
  • wos:000351514500008
  • scopus:84925541793
ISSN
1432-0851
DOI
10.1007/s00262-015-1658-8
language
English
LU publication?
yes
id
ff65d5ba-2257-4884-95d6-a02d1f0ef1f4 (old id 5039791)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25618258?dopt=Abstract
date added to LUP
2015-02-04 16:53:18
date last changed
2017-01-01 03:29:12
@article{ff65d5ba-2257-4884-95d6-a02d1f0ef1f4,
  abstract     = {Tumor cells often evade killing by the complement system by overexpressing membrane-bound complement inhibitors. However, production of soluble complement inhibitors in cells other than hepatocytes was rarely reported. We screened several breast cancer cell lines for expression of soluble complement inhibitor, complement factor I (FI). We also analyzed local production of FI in tissue microarrays with tumors from 130 breast cancer patients by in situ hybridization and immunohistochemistry. We found expression of FI in breast adenocarcinoma cell line MDA-MB-468 and confirmed its functional activity. Expression of FI at mRNA and protein levels was also confirmed in tumor cells and tumor stroma, both in fibroblasts and infiltrating immune cells. Multivariate Cox regression analyses revealed that high expression of FI protein in tumor cells was correlated with significantly shorter cancer-specific survival (HR 2.8; 95 % CI 1.0-7.5; p = 0.048) and recurrence-free survival (HR 3.4; 95 % CI 1.5-7.4; p = 0.002). High FI expression was positively correlated with tumor size (p &lt; 0.001), and Nottingham histological grade (p = 0.015) and associated with estrogen and progesterone receptor status (p = 0.03 and p = 0.009, respectively). Our data show that FI is expressed in breast cancer and is associated with unfavorable clinical outcome.},
  author       = {Okroj, Marcin and Holmquist, Emelie and Nilsson, Elise and Anagnostaki, Lola and Jirström, Karin and Blom, Anna},
  issn         = {1432-0851},
  language     = {eng},
  number       = {4},
  pages        = {467--478},
  publisher    = {Springer},
  series       = {Cancer Immunology and Immunotherapy},
  title        = {Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence.},
  url          = {http://dx.doi.org/10.1007/s00262-015-1658-8},
  volume       = {64},
  year         = {2015},
}