Abstract P3-01-05: Metabolomic analysis of breast cancer cell lines: Clues to the metabolic fingerprint of inflammatory breast cancer
Authors: Mu Z , Brown MV , Fernandez S , Robertson FM , Cristofanilli M 
Published: August 2014

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive type of advanced breast cancer with a poor prognosis and lower survival rate. IBC is characterized by peculiar clinical and biological features and resistance to standard treatments. IBC has shown the capacity to spread early through lymphatic channels and blood vessels causing the specific inflammatory signs. Currently, there are no specific therapeutic options for IBC patients because of very few molecular alterations associated with IBC. Thus, there is an unmet need to identify distinguished features of IBC that differentiate the disease from non-inflammatory breast cancer (nIBC). Metabolomic analysis of cancer cells holds the promise to identify unique chemical fingerprints of important cellular processes. In this study we investigated the global biochemical profiles of IBC and nIBC cells.

METHODS: Three IBC cell lines, SUM190, SUM149, FC-IBC-02, and three nIBC cell lines, MCF-7, MDA-MB-231, MDA-MB-468, with five replicates for each cell line, were analyzed in this study. Metabolomic profiling analysis was performed by Metabolon, Inc (Durham, NC) on the gas chromatography/mass spectroscopy and ultrahigh performance liquid chromatography/mass spectroscopy platforms as previously described (Proc. Natl. Acad. Sci. U. S. A. 108, 3270-3275, 2011). A total of 347 metabolites were detected. Welch's two-sample t-test was used to identify biochemicals that differed significantly between experimental groups (p≤0.001), as well as those approaching significance (0.001&lt;p&lt;0.05).

RESULTS: Comparison of global biochemical profiles for IBC and nIBC cell lines revealed numerous statistically changed metabolites at a p-value threshold of p&lt;0.001. Statistical comparisons also revealed a clear metabolic separation of samples due to cell line differences. Several biochemical pathways emerged as being commonly altered across all IBC cell lines compared to all nIBC cell lines. Notable observations include alterations in inflammatory signaling, energy metabolism, and cell proliferation. Signatures of inflammation were elevated and inflammatory signaling pathways showed activation in IBC cell lines. In energy metabolism, the cellular energy for IBC cells appeared to be derived from amino acid catabolism to a greater extent than in nIBC cells. Furthermore, fatty acids was significantly elevated in IBC cell lines, that may indicate a reduced cellular proliferation and increased glycogen storage in IBC cells. Moreover, an altered methylation and glutathione metabolism were shown in IBC cell lines.

CONCLUSIONS: Our study is the first to demonstrate difference of metabolic profiles between IBC and nIBC cells. Future studies comparing global biochemical profiles in tissue biopsy and blood from IBC and nIBC patients may help to confirm the relevance of these findings in cell lines. Metabolic targets may provide more effective and specific therapeutic strategy for the treatment of IBC patients.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-01-05.