Spatial Analysis of Nucleotide Metabolism: From CRISPR Knockout Cancer Cells to MALDI Imaging of Tumors
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- CRISPR/Cas9, Cancer, MALDI, Metabolism, Nucleotides, Pyrimidines,
- MeSH
- Humans MeSH
- Neoplasms * metabolism MeSH
- Nucleotides MeSH
- Spatial Analysis MeSH
- Pyrimidines MeSH
- Clustered Regularly Interspaced Short Palindromic Repeats * MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Nucleotides MeSH
- Pyrimidines MeSH
Cancer cells depend on nucleotides for proliferation. Inhibition of nucleotide metabolism by antimetabolites is a well-established anticancer therapy. However, resistance and toxicity to antimetabolite treatments reduce their effectiveness. Here, we focus on the pyrimidine de novo synthesis pathway, which is crucial for cancer cell proliferation, yet its pharmacological targeting in cancer has been without much clinical success so far. Hence, it is important to understand how cancer cells cope with the insufficiency of this pathway. Here, we describe a procedure to prepare subcutaneous tumor model deficient in de novo pyrimidine synthesis. For examination of metabolic responses to de novo synthesis blockade in tumors, we propose application of MALDI imaging that allows spatially resolved examination of metabolic responses to de novo synthesis blockade in tumors.
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