Changes in Cancer Cell Metabolism Revealed by Direct Sample Analysis with MALDI Mass Spectrometry

David A. Pirman, Ekem Efuet, Xiao Ping Ding, Yong Pan, Lin Tan, Susan M. Fischer, Raymond N. DuBois, Peiying Yang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Biomarker discovery using mass spectrometry (MS) has recently seen a significant increase in applications, mainly driven by the rapidly advancing field of metabolomics. Instrumental and data handling advancements have allowed for untargeted metabolite analyses which simultaneously interrogate multiple biochemical pathways to elucidate disease phenotypes and therapeutic mechanisms. Although most MS-based metabolomic approaches are coupled with liquid chromatography, a few recently published studies used matrix-assisted laser desorption (MALDI), allowing for rapid and direct sample analysis with minimal sample preparation. We and others have reported that prostaglandin E3 (PGE3), derived from COX-2 metabolism of the omega-3 fatty acid eicosapentaenoic acid (EPA), inhibited the proliferation of human lung, colon and pancreatic cancer cells. However, how PGE3 metabolism is regulated in cancer cells, particularly human non-small cell lung cancer (NSCLC) cells, is not fully understood. Here, we successfully used MALDI to identify differences in lipid metabolism between two human non-small-cell lung cancer (NSCLC) cell lines, A549 and H596, which could contribute to their differential response to EPA treatment. Analysis by MALDI-MS showed that the level of EPA incorporated into phospholipids in H596 cells was 4-fold higher than A549 cells. Intriguingly, H596 cells produced much less PGE3 than A549 cells even though the expression of COX-2 was similar in these two cell lines. This appears to be due to the relatively lower expression of cytosolic phospholipase A2 (cPLA2) in H596 cells than that of A549 cells. Additionally, the MALDI-MS approach was successfully used on tumor tissue extracts from a K-ras transgenic mouse model of lung cancer to enhance our understanding of the mechanism of action of EPA in the in vivo model. These results highlight the utility of combining a metabolomics workflow with MALDI-MS to identify the biomarkers that may regulate the metabolism of omega-3 fatty acids and ultimately affect their therapeutic potentials.

Original languageEnglish (US)
Article numbere61379
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 26 2013
Externally publishedYes

Fingerprint

Metabolism
desorption
lasers
Mass spectrometry
Desorption
Mass Spectrometry
Lasers
Eicosapentaenoic Acid
Cells
mass spectrometry
metabolism
Metabolomics
lung neoplasms
eicosapentaenoic acid
Neoplasms
metabolomics
Omega-3 Fatty Acids
cells
prostaglandins
Non-Small Cell Lung Carcinoma

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pirman, D. A., Efuet, E., Ding, X. P., Pan, Y., Tan, L., Fischer, S. M., ... Yang, P. (2013). Changes in Cancer Cell Metabolism Revealed by Direct Sample Analysis with MALDI Mass Spectrometry. PLoS One, 8(4), [e61379]. https://doi.org/10.1371/journal.pone.0061379

Changes in Cancer Cell Metabolism Revealed by Direct Sample Analysis with MALDI Mass Spectrometry. / Pirman, David A.; Efuet, Ekem; Ding, Xiao Ping; Pan, Yong; Tan, Lin; Fischer, Susan M.; DuBois, Raymond N.; Yang, Peiying.

In: PLoS One, Vol. 8, No. 4, e61379, 26.04.2013.

Research output: Contribution to journalArticle

Pirman, DA, Efuet, E, Ding, XP, Pan, Y, Tan, L, Fischer, SM, DuBois, RN & Yang, P 2013, 'Changes in Cancer Cell Metabolism Revealed by Direct Sample Analysis with MALDI Mass Spectrometry', PLoS One, vol. 8, no. 4, e61379. https://doi.org/10.1371/journal.pone.0061379
Pirman, David A. ; Efuet, Ekem ; Ding, Xiao Ping ; Pan, Yong ; Tan, Lin ; Fischer, Susan M. ; DuBois, Raymond N. ; Yang, Peiying. / Changes in Cancer Cell Metabolism Revealed by Direct Sample Analysis with MALDI Mass Spectrometry. In: PLoS One. 2013 ; Vol. 8, No. 4.
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