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Polar lipid remodeling and increased sulfatide expression are associated with the glioma therapeutic candidates, wild type p53 elevation and the topoisomerase-1 inhibitor, Irinotecan

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Abstract

We report changes in gene and polar lipid expression induced by adenovirus-delivered wild-type (wt) p53 gene and chemotherapy of U87 MG glioblastoma cells, a treatment known to trigger apoptosis and cell cycle arrest. Sulfatides (sulfonated glycolipids) were most highly modulated by wild-type p53 treatment; however, no changes were observed in expression levels of mRNA for genes involved in sulfatide metabolism, indicating post-transcriptional control of sulfatide synthesis. Modulation of the aglycones of GD1 and GM1b was observed in wild-type p53-treated cells. The treatment also leads to an increase in phospholipids such as phosphatidyl inositols, phosphatidyl serines, phosphatidyl glycerols, and phosphatidyl ethanolamines, especially hydroxylated phospholipids. These dramatic changes in the composition of cellular glycolipids in response to p53 gene expression and cytotoxic chemotherapy treatment indicate the large role that they play in cell signaling. The use of the human glioma cell line U87 appears to be an excellent model system both in tissue culture and in intracranial murine xenograft models to further characterize the role of sulfatides in modulating glioma responsivity to therapeutic agents.

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Acknowledgements

Financial support from the National High-Field Fourier Transform Ion Cyclotron Resonance Mass Spectrometry ICR Facility at the National High Magnetic Field Laboratory (NSF DMR 06-54118) and The John C. Merchant Foundation; Live Well, Love Life, Laugh Hard Foundation and the Falk Foundation are also gratefully acknowledged.

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Author notes

  1. Carol L. Nilsson

    Present address: Pfizer Global Research and Development, 10770 Science Center Dr. (CB2), San Diego, CA, 92121, USA

Authors and Affiliations

  1. National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, 32310, USA

    Huan He, Carol L. Nilsson, Mark R. Emmett & Alan G. Marshall

  2. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, 32306-4390, USA

    Huan He, Mark R. Emmett & Alan G. Marshall

  3. Falk Center for Molecular Therapeutics, Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

    Roger A. Kroes & Joseph R. Moskal

  4. M.D. Anderson Cancer Center, Department of Neuro-oncology, Houston, TX, USA

    Yongjie Ji, Howard Colman, Frederick F. Lang & Charles A. Conrad

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Supplementary Table 1

Ion relative abundances for polar lipids from U87 MG cells. (PDF 78 kb)

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He, H., Nilsson, C.L., Emmett, M.R. et al. Polar lipid remodeling and increased sulfatide expression are associated with the glioma therapeutic candidates, wild type p53 elevation and the topoisomerase-1 inhibitor, Irinotecan. Glycoconj J 27, 27–38 (2010). https://doi.org/10.1007/s10719-009-9249-6

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