Quantitative analysis of 5′-deoxy-5′-methylthioadenosine in melanoma cells by liquid chromatography-stable isotope ratio tandem mass spectrometry

Stevens, Axel Peter; Dettmer, Katja; Wallner, Susanne; Bosserhoff, Anja‐Katrin; Oefner, Peter J.

doi:10.1016/j.jchromb.2008.10.038

Cited by 23 publications

(14 citation statements)

References 17 publications

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“…Extraction was carried out in methanol as described (72). Frozen cell pellets were extracted by the addition of 600 μL HPLC grade methanol (Acros) and allowed to thaw on ice.…”

Section: Methodsmentioning

confidence: 99%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Genome-wide association studies can identify common differences that contribute to human phenotypic diversity and disease. When genome-wide association studies are combined with approaches that test how variants alter physiology, biological insights can emerge. Here, we used such an approach to reveal regulation of cell death by the methionine salvage pathway. A common SNP associated with reduced expression of a putative methionine salvage pathway dehydratase, apoptotic protease activating factor 1 (APAF1)-interacting protein (APIP), was associated with increased caspase-1-mediated cell death in response to Salmonella. The role of APIP in methionine salvage was confirmed by growth assays with methionine-deficient media and quantitation of the methionine salvage substrate, 5′-methylthioadenosine. Reducing expression of APIP or exogenous addition of 5′-methylthioadenosine increased Salmonellae-induced cell death. Consistent with APIP originally being identified as an inhibitor of caspase-9-dependent apoptosis, the same allele was also associated with increased sensitivity to the chemotherapeutic agent carboplatin. Our results show that common human variation affecting expression of a single gene can alter susceptibility to two distinct cell death programs. Furthermore, the same allele that promotes cell death is associated with improved survival of individuals with systemic inflammatory response syndrome, suggesting a possible evolutionary pressure that may explain the geographic pattern observed for the frequency of this SNP. Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology.HapMap | lymphoblastoid | pyroptosis | quantitative trait | polygenic adaptation

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“…Extraction was carried out in methanol as described (72). Frozen cell pellets were extracted by the addition of 600 μL HPLC grade methanol (Acros) and allowed to thaw on ice.…”

Section: Methodsmentioning

confidence: 99%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…MTA was quantified using a validated protocol that included an in‐house synthesized stable isotope‐labeled MTA standard .…”

Section: Methodsmentioning

confidence: 99%

“…Further mechanisms, by which tumors impair T cell function, include depletion of arginine and production of NO . Other metabolites such as 5′‐deoxy‐5′‐methylthioadenosine (MTA), a by‐product of polyamine biosynthesis, promote cancer cell growth by inducing expression of matrix metalloproteinases in both, cancer and stromal cells, thereby facilitating tumor angiogenesis, invasion, and metastatic spread .…”

Section: Introductionmentioning

confidence: 99%

Distinct metabolic differences between various human cancer and primary cells

et al. 2013

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Recent years have seen resurging interest in cancer cell metabolism and the role of secreted cancer metabolites in modulating the tumor stroma. Using a combination of nontargeted and targeted LC and GC-MS methods, the exometabolomes of three leukemia, two melanoma, three renal cell carcinoma, two colorectal adenocarcinoma, four hepatocellular carcinoma, three breast cancer, two bladder carcinoma, and one glioblastoma cell line, as well as five primary cultures of human melanocytes, hepatocytes, monocytes, CD4 and CD8 lymphocytes, that had been all cultivated under identical conditions, were investigated. Unsupervised affinity propagation clustering of the metabolic footprints yielded five distinct clusters that grouped the investigated cell cultures mainly according to the tissue of origin. A common expected feature of all neoplastic cells was high lactate production. Extracellular arginine and nicotinamide were major discriminants between normal and neoplastic hepatocytes. Further, significant differences in the assimilation of di- and tripeptides were observed. This finding appears to underscore the importance of peptides for meeting the increased bioenergetic and biosynthetic demands of many cancers.

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“…Quantitative determination was performed in multiple‐reaction monitoring (MRM) mode using the following ion transitions: m/z 298.2 (M + H+) to m/z 136.1 (product ion) for endogenous MTA, and m/z 303.2 (M + H+) to m/z 136.1 (product ion) for the 13 C 5 ‐labeled internal MTA standard (Stevens et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Direct and tumor microenvironment mediated influences of 5′‐deoxy‐5′‐(methylthio)adenosine on tumor progression of malignant melanoma

Stevens

Spangler

Wallner

et al. 2008

J of Cellular Biochemistry

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Recent studies have shown that a loss of methylthioadenosine phosphorylase (MTAP) gene expression exerts a tumor-promoting effect, including induction of invasiveness, enhanced cell proliferation, and resistance against cytokines. To date, the molecular mechanisms underlying these effects remain unknown. Since the loss of MTAP expression resulted in induced secretion of 5'-deoxy-5'-(methylthio)adenosine (MTA), we hypothesized that MTA might modulate the observed effects. We first determined MTA levels produced by tumor cells in vitro and in situ by means of stable isotope dilution liquid chromatography tandem mass spectrometry. Subsequently, we revealed induction of matrix metalloproteinase (MMP) and growth factor gene expression in melanoma cells accompanied by enhanced invasion and vasculogenic mimicry. In addition, MTA induced the secretion of basis fibroblast growth factor (bFGF) and MMP3 from fibroblasts and the upregulation of activator protein-1 (AP-1) activity in melanoma cells and fibroblasts. In summary, we demonstrated a tumor-supporting role of MTA.

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Quantitative analysis of 5′-deoxy-5′-methylthioadenosine in melanoma cells by liquid chromatography-stable isotope ratio tandem mass spectrometry

Cited by 23 publications

References 17 publications

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Distinct metabolic differences between various human cancer and primary cells

Direct and tumor microenvironment mediated influences of 5′‐deoxy‐5′‐(methylthio)adenosine on tumor progression of malignant melanoma

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