1H-NMR-based metabolic profiling of a colorectal cancer CT-26 lung metastasis model in mice

Abstract

Lung metastasis is an important cause for the low 5-year survival rate of colorectal cancer patients. Understanding the metabolic profile of lung metastasis of colorectal cancer is important for developing molecular diagnostic and therapeutic approaches. We carried out the metabonomic profiling of lung tissue samples on a mouse lung metastasis model of colorectal cancer using 1H-nuclear magnetic resonance (1H-NMR). The lung tissues of mice were collected at different intervals after marine colon cancer cell line CT-26 was intravenously injected into BALB/c mice. The distinguishing metabolites of lung tissue were investigated using 1H-NMR-based metabonomic assay, which is a highly sensitive and non-destructive method for biomarker identification. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to analyze 1H-NMR profiling data to seek potential biomarkers. All of the 3 analyses achieved excellent separations between the normal and metastasis groups. A total of 42 metabolites were identified, ~12 of which were closely correlated with the process of metastasis from colon to lung. These altered metabolites indicated the disturbance of metabolism in metastatic tumors including glycolysis, TCA cycle, glutaminolysis, choline metabolism and serine biosynthesis. Our findings firstly identified the distinguishing metabolites in mouse colorectal cancer lung metastasis models, and indicated that the metabolite disturbance may be associated with the progression of lung metastasis from colon cancer. The altered metabolites may be potential biomarkers that provide a promising molecular approach for clinical diagnosis and mechanistic study of colorectal cancer with lung metastasis.

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study

“…In previous studies using 1 H-NMR-based metabolic profiling, elevated levels of phospholipid precursors, choline, phosphocholine and phosphoethanolamine, were found in both human CRC tissues [33] and CRC CT26 cell line [34]. In the LC-MS/MS study conducted by Moro et al, the levels of SM in breast cancer were significantly higher than in peritumor tissue and normal tissue [35].…”

The therapeutic potential of losartan in lung metastasis of colorectal cancer

“…The animals were kept under standard conditions which were approved by the Institute Animal Ethics Committee of the Mashhad University of Medical Sciences (humidity of 54 ± 2 %, temperature 22 ± 2 °C and 12 h light/dark cycle). Mice were injected with 2x10⁶ CT26 cells by intravenous tail injection and were then treated from 24 hours after the cell injection for 10 days (Li et al, 2017[ 15 ]). The animals were randomly divided into four groups as follows (n = 6 in each group): 1) a control group, 2) a 5-FU only group (treated with 5 mg/kg every other day, intraperitoneally (ip)) (Marjaneh et al, 2018[ 17 ]), 3) a losartan group (treated with 90 mg/kg/day, ip), 4) a combination group (treated with 5mg/kg 5-FU every other day, ip and losartan 90 mg/kg/day, ip).…”

Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model

“…Finally, the strong DMA depletion induced by cDDP may relate to disturbances in methylamine metabolism, and to choline levels ( Figure 6 ). DMA variations have been observed in several pancreatic and colorectal cancers [ 76 , 77 ], and indeed DMA has been reported to decrease after treatment with epicatechin [ 78 ]. It is thus possible that DMA may serve as an indicator of response to cDDP therapy.…”