Summary of Study ST003718
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002307. The data can be accessed directly via it's Project DOI: 10.21228/M8F244 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003718 |
| Study Title | Metabolomics of plasma and tumor interstitial fluid (TIF) of tumors from Lyz2-Cre(+/+);Arg1(fl/fl) mice. |
| Study Type | Metabolomics |
| Study Summary | Mice or the genotype Lyz2-Cre(-/-);Arg1(fl/fl) or Lyz2-Cre(+/+);Arg1(fl/fl) were implanted with PDAC tumors and allowed to grow for 4 weeks. After 3 weeks of growth, mice were placed on 8% deuterated water for fatty acid synthesis analysis. To confirm that Lyz2-Cre(+/+);Arg1(fl/fl) had plasma concentrations of arginine, we performed metabolomics analysis on the plasma and tumor interstitial fluid of tumors from each mouse genotype. We found that arginine concentrations rose to plasma levels in Lyz2-Cre(+/+);Arg1(fl/fl) mice. This confirmed that this mouse model allows us to assay arginine deprivation in vivo. |
| Institute | University of Chicago |
| Department | Ben May Department for Cancer Research |
| Laboratory | Muir Lab |
| Last Name | Jonker |
| First Name | Patrick |
| Address | 929 E 57th St. Chicago IL, 60637 |
| pbjonker@uchicago.edu | |
| Phone | 6162884547 |
| Submit Date | 2025-02-09 |
| Num Groups | 10 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-02-14 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002307 |
| Project DOI: | doi: 10.21228/M8F244 |
| Project Title: | Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis |
| Project Type: | Lipidomics |
| Project Summary: | Nutrient limitation is a characteristic feature of poorly perfused tumors. These changes in nutrient availability impose metabolic constraints and perturb metabolic pathways in cancer cells, in contrast to cells in well-perfused tissues. Consequently, targeting the metabolic dependencies created by tumor microenvironmental constraints may be a promising antineoplastic therapeutic approach. To identify these adaptations, we challenged pancreatic cancer cell lines (mouse Pancreatic Ductal Adenocarcinoma - PDAC) with pathophysiological nutrient levels and analyzed changes to cell metabolism. Here, we report that arginine limitation in pancreatic cancer perturbs saturated and monounsaturated fatty acid synthesis by suppressing the lipogenic transcription factor SREBP1. Synthesis of these acyl species is critical to maintaining a balance of saturated, monounsaturated, and polyunsaturated fatty acids in cellular membranes. We found that, as a consequence of the loss of fatty acid synthesis, pancreatic cancer cells were unable to maintain balanced lipidomes when exposed to polyunsaturated fatty acids, leading to cell death by ferroptosis. Importantly, we found orally administering oils rich in polyunsaturated fats reduces tumor burden in mice with pancreatic cancer. In sum, this study illustrates that arginine restriction in the tumor microenvironment alters pancreatic cancer cells by perturbing lipid synthesis, making them sensitive to supplementation with polyunsaturated fats. |
| Institute: | University of Chicago |
| Last Name: | Jonker |
| First Name: | Patrick |
| Address: | 929 E 57th St. Chicago IL, 60637 |
| Email: | pbjonker@uchicago.edu |
| Phone: | 6162884547 |
Subject:
| Subject ID: | SU003850 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Genotype |
|---|---|---|---|
| SA406707 | Plasma_7 | Plasma | Lyz2-Cre+/+ Arg1fl/fl |
| SA406708 | Plasma_10 | Plasma | Lyz2-Cre+/+ Arg1fl/fl |
| SA406709 | Plasma_14 | Plasma | Lyz2-Cre+/+ Arg1fl/fl |
| SA406710 | Plasma_5 | Plasma | Lyz2-Cre+/+ Arg1fl/fl |
| SA406711 | Plasma_6 | Plasma | Lyz2-Cre+/+ Arg1fl/fl |
| SA406712 | Plasma_9 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406713 | Plasma_8 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406714 | Plasma_1 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406715 | Plasma_4 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406716 | Plasma_2 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406717 | Plasma_11 | Plasma | Lyz2-Cre-/- Arg1fl/fl |
| SA406718 | TIF_05 | Tumor interstitial fluid | Lyz2-Cre+/+ Arg1fl/fl |
| SA406719 | TIF_06 | Tumor interstitial fluid | Lyz2-Cre+/+ Arg1fl/fl |
| SA406720 | TIF_07 | Tumor interstitial fluid | Lyz2-Cre+/+ Arg1fl/fl |
| SA406721 | TIF_10 | Tumor interstitial fluid | Lyz2-Cre+/+ Arg1fl/fl |
| SA406722 | TIF_14 | Tumor interstitial fluid | Lyz2-Cre+/+ Arg1fl/fl |
| SA406723 | TIF_02 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| SA406724 | TIF_04 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| SA406725 | TIF_08 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| SA406726 | TIF_09 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| SA406727 | TIF_11 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| SA406728 | TIF_01 | Tumor interstitial fluid | Lyz2-Cre-/- Arg1fl/fl |
| Showing results 1 to 22 of 22 |
Collection:
| Collection ID: | CO003843 |
| Collection Summary: | 5 µL of TIF or plasma sample was mixed with 45 µL of ice-cold acetonitrile containing stable isotope labeled amino acid mix from Cambridge Isotope Labs(MSK-A1-1.2) as internal standards. Only 3 uL were analyzed for sample "TIF_07" due to low sample volume from TIF extraction. Samples were vortexed, incubated on ice for 20 minutes, centrifuged at 20,000g for 20mins at 4°C and the supernatant was transferred to an autosampler vial for LC-MS analysis. Arginine calibration curves was prepared from 0.1µ-500 µM levels. |
| Sample Type: | Blood (plasma), Tumor interstitial fluid |
Treatment:
| Treatment ID: | TR003859 |
| Treatment Summary: | Mice were injected with mPDAC3 orthotopic tumors. After 4 weeks of tumor growth, tumor interstitial fluid and plasma were extracted for analysis of arginine levels. |
Sample Preparation:
| Sampleprep ID: | SP003856 |
| Sampleprep Summary: | 5 µL of TIF or plasma sample was mixed with 45 µL of ice-cold acetonitrile containing stable isotope labeled amino acid mix from Cambridge Isotope Labs(MSK-A1-1.2) as internal standards. Samples were vortexed, incubated on ice for 20 minutes, centrifuged at 20,000g for 20mins at 4°C and the supernatant was transferred to an autosampler vial for LC-MS analysis. Arginine calibration curves was prepared from 0.1µ-500 µM levels. |
Chromatography:
| Chromatography ID: | CH004630 |
| Instrument Name: | Thermo Fisher IQ-X |
| Column Name: | Waters XBridge BEH Amide (150 x 2.1mm, 2.5um) |
| Column Temperature: | 40 |
| Flow Gradient: | 0min: 95% B, 9min: 70% B, 9.75min: 40% B, 12min: 40% B, 13min: 30% B, 14min: 30%B, 14.1min: 10% B,17min: 10% B, 17.5min: 95% B, 22min: 95% B |
| Flow Rate: | 0.3 mL/min |
| Solvent A: | 90% water/5% acetonitrile/5% methanol; 0.2% acetic acid; 20mM ammonium acetate |
| Solvent B: | 90% acetonitrile/10% water; 0.2% acetic acid; 10mM ammonium acetate |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN006099 |
| Laboratory Name: | University of Chicago Metabolomics Platform |
| Analysis Type: | MS |
| Operator Name: | Hardik Shah |
| Chromatography ID: | CH004630 |
| Num Factors: | 4 |
| Num Metabolites: | 2 |
| Units: | Peak area |
