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Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.

ABSTRACT: Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here, we investigated the effect of HT on the immune response toward breast tumor antigens.Plasmas collected 0-10 months prior to diagnosis of ER+ breast cancer from 190 postmenopausal women and 190 controls that participated in the Women's Health Initiative Observational Study were analyzed for the effect of HT on IgG reactivity against arrayed proteins from MCF-7 or SKBR3 breast cancer cell line lysates following extensive fractionation.HT user cases exhibited significantly reduced autoantibody reactivity against arrayed proteins compared to cases who were Not Current users. An associated reduced level of IL-6 and other immune-related cytokines was observed among HT users relative to nonusers.Our findings suggest occurrence of a global altered immune response to breast cancer-derived proteins associated with HT. Thus a full understanding of factors that modulate the immune response is necessary to translate autoantibody panels into clinical applications.

SUBMITTER: Chao T

PROVIDER: S-EPMC4681300 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.

Chao Timothy T Ladd Jon J JJ Qiu Ji J Johnson Melissa M MM Israel Rebecca R Chin Alice A Wang Hong H Prentice Ross L RL Feng Ziding Z Disis Mary L ML Hanash Samir S

Proteomics. Clinical applications 20130510 5-6

<h4>Purpose</h4>Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here, we investigated the effect of HT on the immune response toward breast tumor antigens.<h4>Experimental design</h4>Plasmas collected 0-10 months prior to diagnosis of ER+ breast cancer from 190 postmenopausal women and 190 controls that part ...[more]

PMID: 23401414

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Project description:The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p?0.05) in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS) as heat shock protein 27 (HSP27), translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27 levels using natural alternative agents, as resveratrol, may be an effective adjuvant in breast cancer therapy.

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Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.

Publications

Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.

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