Assessment of the molecular expression and structure of gangliosides in brain metastasis of lung adenocarcinoma by an advanced approach based on fully automated chip-nanoelectrospray mass spectrometry.
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| Abstract |
Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di-O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.
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| Authors | Alina D Zamfir, Alina Serb, Željka Vukeli, Corina Flangea, Catalin Schiopu, Dragana Fabris, Svjetlana Kalanj-Bognar, Florina Capitan, Eugen Sisu |
| Journal | Journal of the American Society for Mass Spectrometry (J Am Soc Mass Spectrom) Vol. 22 Issue 12 Pg. 2145-59 (Dec 2011) ISSN: 1879-1123 [Electronic] United States |
| PMID | 22002228 (Publication Type: Journal Article) |
| Copyright | © American Society for Mass Spectrometry, 2011 |
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