Background: To date, because of the complexity and heterogeneity of breast cancer, no individual model recapitulates all aspects of this disease. Since both the mammary and salivary glands are exocrine glands and that the literature has shown cross-talk between the two glands, we hypothesize that, secondary to breast cancer, the malignancy's rapid growth alters the proteomic content of the tissue microenvironment and that these changes may manifest in up or down regulation of salivary protein concentrations, which can be used as a sentinel body fluid for breast cancer modeling. Verification that salivary proteomic content can be used to model breast cancer progression employing HER2 biology would provide strong support for immediate translational testing in clinical trial settings that would further be accelerated with the use of saliva-based testing as one of the most easily accessible body fluids.
Objective: The objective of this study was to compare the salivary protein profiles of pooled saliva specimens from individuals diagnosed with ductal carcinoma of the breast with and without HER2/neu overexpression as a potential alternate to current HER2/neu assessment methodologies.
Methods: Pooled (n=10 subjects/pooled specimen) stimulated whole saliva specimens from women were analyzed. One pooled specimen was from healthy women, another was from women diagnosed with Stage IIa (T2N0M0) invasive ductal carcinoma (IDC) without positive HER2/neu receptor status. A third pooled specimen was from women diagnosed with Stage IIa (T2N0M0) IDC with a positive HER2/neu receptor status. Isotopically tagging proteins in the tumor groups and comparing them to the healthy control group measured differential expression of proteins. Experimentally, saliva from each of the pooled samples was trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase (C18) capillary chromatography on an LC-MS/MS mass spectrometer equipped with an LC-Packings HPLC. Results: The results of the analyses yielded approximately 174 differentially expressed proteins in the saliva specimens. There were 20 proteins unique to HER2/neu positive receptor status and 28 proteins that were unique to HER2/neu negative status. Conclusions: The study suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be differently expressed in the presence of HER2/neu positive receptor status. It also provides support to the novel idea of using salivary secretions to study breast cancer progression
Citation Format: Charles F. Streckfus. Salivary proteome as an in vivo model to study breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5232. doi:10.1158/1538-7445.AM2013-5232