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

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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 < 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.

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Abbreviations

ATCC:

American Type Culture Collection

CDCC:

Complement-dependent cell cytotoxicity

CI:

Confidence interval

CSS:

Cancer-specific survival

C4BP:

C4b-binding protein

ER:

Estrogen receptor

FH:

Complement factor H

FI:

Complement factor I

Her2:

Epidermal growth factor receptor 2

HR:

Hazard ratio

MOPS:

3-(N-morpholino)propanesulfonic acid

NHG:

Nottingham histological grade

NSCLC:

Non-small cell lung cancer

PR:

Progesterone receptor

PVDF:

Polyvinylidene difluoride

RFS:

Recurrence-free survival

SDS–PAGE:

Sodium dodecyl sulfate, polyacrylamide gel electrophoresis

TMA:

Tissue microarray

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Acknowledgments

We are grateful to Dr. Linda Werner-Hartman for help with statistical analyses, to Prof. Tommy Andersson for sharing breast cancer cell lines, Viktor Fransson for technical help with purification of FI antibodies and to Dr. Sara Nilsson for producing recombinant FI used for affinity purification of antibodies. This work was supported by the Swedish Cancer Society (to Anna Blom), the Swedish Research Council grants (K2012-66X-14928-09-5 to Anna Blom and K2010-80X-21514-01-4 to Marcin Okroj), grant for clinical research (ALF, to Anna Blom) and the Foundations of Österlund (to Anna Blom), Greta and Johan Kock (to Anna Blom), Malmo Cancer (to Marcin Okroj and Anna Blom), Tore Nilsson (to Marcin Okroj), Knut and Alice Wallenberg (to Anna Blom) and Inga-Britt and Arne Lundberg (to Anna Blom), as well as grants from the Skåne University Hospital (to Anna Blom and Marcin Okroj).

Conflict of interest

Authors declare no conflict of interest.

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Authors and Affiliations

  1. Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Inga Maria Nilssons Street 53, Floor 4, 20502, Malmö, Sweden

    Marcin Okroj, Emelie Holmquist & Anna M. Blom

  2. Laboratory Medicine, Clinical Chemistry, Region Skåne, Inga Maria Nilssons Street 53, 20502, Malmö, Sweden

    Marcin Okroj

  3. Section of Pathology, Department of Laboratory Medicine Malmö, Lund University, Jan Waldenström Street 59, 20502, Malmö, Sweden

    Elise Nilsson

  4. Laboratory Medicine, Clinical Pathology, Region Skåne, Jan Waldenström Street 59, 20502, Malmö, Sweden

    Lola Anagnostaki

  5. Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Sölvegatan 25, 22185, Lund, Sweden

    Karin Jirström

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  1. Marcin Okroj
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Correspondence to Anna M. Blom.

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Okroj, M., Holmquist, E., Nilsson, E. et al. Local expression of complement factor I in breast cancer cells correlates with poor survival and recurrence. Cancer Immunol Immunother 64, 467–478 (2015). https://doi.org/10.1007/s00262-015-1658-8

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  • DOI: https://doi.org/10.1007/s00262-015-1658-8

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