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Identification of lipid biomarkers of metastatic potential and gene expression (HER2/p53) in human breast cancer cell cultures using ambient mass spectrometry

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Abstract

In breast cancer, overexpression of human epidermal growth factor receptor 2 (HER2) correlates with overactivation of lipogenesis, mutation of tumor suppressor p53, and increased metastatic potential. The mechanisms through which lipids mediate p53, HER2, and metastatic potential are largely unknown. We have developed a desorption electrospray ionization mass spectrometry (DESI-MS) method to identify lipid biomarkers of HER2/p53 expression, metastatic potential, and disease state (viz. cancer vs. non-cancerous) in monolayer and suspension breast cancer cell cultures (metastatic potential: MCF-7, T-47D, MDA-MB-231; HER2/p53: HCC2218 (HER2+++/p53+), HCC1599 (HER2−/p53−), HCC202 (HER2++/p53−), HCC1419 (HER2+++/p53−) HCC70 (HER2−/p53+++); non-cancerous: MCF-10A). Unsupervised principal component analysis (PCA) of DESI-MS spectra enabled identification of twelve lipid biomarkers of metastatic potential and disease state, as well as ten lipids that distinguish cell lines based on HER2/p53 expression levels (> 200 lipids were identified per cell line). In addition, we developed a DESI-MS imaging (DESI-MSI) method for mapping the spatial distribution of lipids in metastatic spheroids (MDA-MB-231). Of the twelve lipids that correlate with changes in the metastatic potential of monolayer cell cultures, three were localized to the necrotic core of spheroids, indicating a potential role in promoting cancer cell survival in nutrient-deficient environments. One lipid species, which was not detected in monolayer MDA-MB-231 cultures, was spatially localized to the periphery of the spheroid, suggesting a potential role in invasion and/or proliferation. These results demonstrate that combining DESI-MS/PCA of monolayer and suspension cell cultures with DESI-MSI of spheroids is a promising approach for identifying lipid biomarkers of specific genotypes and phenotypes, as well as elucidating the potential function of these biomarkers in breast cancer.

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Acknowledgments

 The authors wish to acknowledge Nova Southeastern University (NSU) and the University of Illinois at Urbana-Champaign (UIUC) for financial support (all experiments were performed at UIUC). We would also thank Dr. Sandy McMasters of the UIUC Cell Media Facility. We also acknowledge the assistance of Chethani Chitraacharige (NSU).

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Authors and Affiliations

  1. Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA

    Heather M. Robison, Corryn E. Chini, Troy J. Comi, Seung Woo Ryu & Richard H. Perry

  2. Department of Chemistry and Physics, Nova Southeastern University, Fort Lauderdale, FL, 33314, USA

    Elaine Ognjanovski & Richard H. Perry

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  1. Heather M. Robison
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Correspondence to Richard H. Perry.

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Robison, H.M., Chini, C.E., Comi, T.J. et al. Identification of lipid biomarkers of metastatic potential and gene expression (HER2/p53) in human breast cancer cell cultures using ambient mass spectrometry. Anal Bioanal Chem 412, 2949–2961 (2020). https://doi.org/10.1007/s00216-020-02537-4

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  • DOI: https://doi.org/10.1007/s00216-020-02537-4

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