Format

Send to

Choose Destination
Cancer Res. 2015 Aug 15;75(16):3246-54. doi: 10.1158/0008-5472.CAN-15-0248. Epub 2015 Jun 18.

An Autoimmune Response Signature Associated with the Development of Triple-Negative Breast Cancer Reflects Disease Pathogenesis.

Author information

1
MD Anderson Cancer Center, Houston, Texas.
2
Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Tumor Vaccine Group, University of Washington, Seattle, Washington.
4
Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
5
Division of Hematology/Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
6
MD Anderson Cancer Center, Houston, Texas. shanash@mdanderson.org.

Abstract

The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple-negative breast cancer (TNBC) in the before diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected before clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in estrogen receptor(+) breast cancer. Importantly, autoantibodies directed against networks involving BRCA1, TP53, and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC before diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected before occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig-bound proteins yielding a predominance of cytokeratins, including several associated with a mesenchymal/basal phenotype among cases compared with controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC.

PMID:
26088128
PMCID:
PMC4676710
DOI:
10.1158/0008-5472.CAN-15-0248
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center