2022
DOI: 10.1002/cpt.2633
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Quantitative Proteomics of Hepatic Drug‐Metabolizing Enzymes and Transporters in Patients With Colorectal Cancer Metastasis

Abstract: The impact of liver cancer metastasis on protein abundance of 22 drug-metabolizing enzymes (DMEs) and 25 transporters was investigated using liquid chromatography-tandem accurate mass spectrometry targeted proteomics. Microsomes were prepared from liver tissue taken from 15 healthy individuals and 18 patients with cancer (2 primary and 16 metastatic). Patient samples included tumors and matching histologically normal tissue. The levels of cytochrome P450 (CYPs 2B6, 2D6, 2E1, 3A4, and 3A5) and uridine 5′-diphos… Show more

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Cited by 11 publications
(16 citation statements)
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“…Liver tissue was prepared into microsomes, as previously described ( 28 30 ). Briefly, liver tissue was homogenized using a Fisherbrand 150 Handheld Homogenizer (Thermo Fisher Scientific, UK) in homogenization buffer (150 mM KCl, 2 mM EDTA, 50 mM Tris, 1 mM dithiothreitol, and EDTA-free protease inhibitor cocktail, pH 7.4) at 10 ml per gram of liver tissue.…”
Section: Methodsmentioning
confidence: 99%
“…Liver tissue was prepared into microsomes, as previously described ( 28 30 ). Briefly, liver tissue was homogenized using a Fisherbrand 150 Handheld Homogenizer (Thermo Fisher Scientific, UK) in homogenization buffer (150 mM KCl, 2 mM EDTA, 50 mM Tris, 1 mM dithiothreitol, and EDTA-free protease inhibitor cocktail, pH 7.4) at 10 ml per gram of liver tissue.…”
Section: Methodsmentioning
confidence: 99%
“…In addition to their presence in normal tissues, the expression of these transporters has been found to be up- or down-regulated in certain cancers ( Table 1 ). Thus, OATP1A2 absolute protein expression has been found to be lower in liver cancer metastases compared to in histologically normal tissue [ 55 ]. Moreover, OATP1A2/SLCO1A2 and OATP1B3/SLCO1B3 mRNA and protein expression was significantly higher in malignant breast cancer tissue as compared to the surrounding non-malignant tissue [ 56 , 57 ].…”
Section: Slc Transporters In Cancermentioning
confidence: 99%
“…Liver-specific OATP1B1 and OATP1B3 play important roles in the elimination of metabolites and xenobiotics from the body. However, liver cancers such as hepatocellular carcinoma and colorectal carcinoma liver metastases have an intrinsically low expression of these transporters [ 55 , 60 ], as they do not transport substrates, which are necessary for the survival of this type of cancer cell. This is a challenge in terms of drug delivery into liver tumors, as many drugs are substrates of OATP1B1 and/or OATP1B3.…”
Section: Slc Transporters In Cancermentioning
confidence: 99%
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