Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma

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Abstract

Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MALDIMSI) allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts. In combination with tandem mass spectrometry GM3 (d18:1/C24:0) was identified as the most abundant ganglioside species in the glioma allotransplant. By contrast, mouse xenografts of human medulloblastoma were characterized by prominent expression of the ganglioside GM2 (d18:0/C18:0). Together, these data demonstrate that tissue-based MALDI-MSI of gangliosides is able to discriminate between different brain tumors and may be a useful clinical tool for their classification and grading.

Figures

  • Fig 1. MALD-MSI of GM1 and GD1 in adult rat brain. MSI and mass spectra of GM1/GD1-sialic acid (H-) d18:1 (m/z 1545) and 20:1 (m/z 1573), GD1 ([M-H]2-) d18:1 (m/z 1874) and 20:1 (m/z 1886) in healthy adult Wistar rat brain. Intensities of the ions are represented in color based on the intensity scale provided. Arrows indicate the peaks visualized in MSI. GD1-sa = GD1-sialic acid.
  • Fig 2. MALD-MSI of GM1 and GD1 in intracranial allografts of rat glioma. (A) MSI of GM1/GD1-sialic acid (H-) d18:1 (m/z 1545) and 20:1 (m/z 1573), GD1 [M+Na-2H] d18:1 (m/z 1874) and 20:1 (m/z 1886). Intensities of the ions are represented in color based on the intensity scale provided. (B) Distribution of GM1 and NRP-1 by immunostaining with CTB and anti-NRP1 antibodies, respectively, in intracranial allografts of rat glioma. Circles indicate the position of the xenograft. Scale bar: 5 mm. GD1-sa = GD1-sialic acid.
  • Fig 3. MALD-MSI of GM3 in intracranial allografts of rat glioma. (A) MSI of GM3 (H-) d18:1 24:0 (m/z 1264) and d18:0 20:1 (m/z 1208) in intracranial allografts of rat glioma. Intensities of the ions are represented in color based on the intensity scale provided. (B) Molecular histology distribution of GM1/GD1-sialic acid (d18:1/C18:0) and GM3 (d18:1/ C24:0) in intracranial allografts of rat glioma. Red squares indicate the position of the glioma xenograft. Scale bar: 5 mm. GD1-sa = GD1-sialic acid.
  • Fig 4. MALD-MSI of GM1 and GD1 in adult mouse brain. (A) MSI and mass spectra of GM1/GD1-sialic acid (H-) d18:1 (m/z 1545) and 20:1 (m/z 1573), GD1 [M+Na-2H] d18:1 (m/z 1874) and 20:1 [M+K-2H] (m/z 1902). Intensities of the ions are represented in color based on the intensity scale provided. Arrows indicate the peaks visualized in MSI. (B) Overlap of the distribution of GM1/GD1-sialic acid and GD1 species in healthy adult mouse brain. Scale bar: 4 mm. GD1-sa = GD1-sialic acid.
  • Fig 5. MALD-MSI of gangliosides in intracranial xenografts of human medulloblastoma. (A) MSI of GM1/GD1-sialic acid (H-) d18:1 (m/z 1545) and 20:1 (m/z 1573), GD1 ([M-H]2-) d18:1 (m/z 1874) and 20:1 (m/ z 1902), GM3 (H-) d18:1 c24:0 (m/z 1264) and GM2 (H-) d18:0 c18:0 (m/z 1385) in intracranial xenografts of human medulloblastoma. Intensities of the ions are represented in color based on the intensity scale provided. (B) Mass spectra of GM2 (d18:0/C18:0) in intracranial xenografts of human medulloblastoma. (C) Distribution of Neuropilin-1 by immunostaining with anti-NRP1 antibodies in intracranial xenografts of human medulloblastoma. The insert is a magnification 40 x of the glioma area. (D) Molecular histology distribution of GM2 (d18:0/C18:0) in intracranial xenografts of human medulloblastoma. Squares indicate the position of the medulloblastoma graft. Scale bar: 4 mm. GD1-sa = GD1-sialic acid.

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APA

Ermini, L., Morganti, E., Post, A., Yeganeh, B., Caniggia, I., Leadley, M., … Post, M. (2017). Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma. PLoS ONE, 12(5). https://doi.org/10.1371/journal.pone.0176254

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