Naslov
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

Autori
Zamfir, Alina D. ; Serb, Alina ; Vukelić, Željka ; Flangea, Corina ; Schiopu, Catalin ; Fabris, Dragana ; Kalanj-Bognar, Svjetlana ; Capitan, Florina ; Sisu, Eugen

Izvornik
Journal of the American Society for Mass Spectrometry (1044-0305) 22 (2011), 12; 2145-2159

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Quadrupole time-of-flight tandem mass spectrometry; Chip-nanoelectrospray; Gangliosides; Lung adenocarcinoma; Brain metastasis

Sažetak
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 agematched 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 Nacetylneuraminic 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 collisioninduced 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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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