Summary of Study ST002529

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 PR001627. The data can be accessed directly via it's Project DOI: 10.21228/M8D434 This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST002529
Study TitleIn vivo 15N2-glutamine tracing by jugular vein infusion in PDAC-tumor bearing Lyz2-Arg1 and control mice
Study SummaryWe assessed the relative levels of urea cycle related metabolites in PDAC tumors in Lyz2-Cre+/+; Arg1fl/fl compared to Arg1fl/fl control host animals.
Institute
University of Chicago
Last NameApiz Saab
First NameJuan
Address929 E. 57th St.
Emailjapizsaab@uchicago.edu
Phone7738346506
Submit Date2023-03-24
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-04-13
Release Version1
Juan Apiz Saab Juan Apiz Saab
https://dx.doi.org/10.21228/M8D434
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001627
Project DOI:doi: 10.21228/M8D434
Project Title:Pancreatic tumors activate arginine biosynthesis to adapt to myeloid-driven amino acid stress
Project Summary:Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs to maintain survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors (Sullivan et al., 2019a). Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling study of PDAC metabolism under physiological nutrition. We show that PDAC cells cultured in TIFM, compared to standard laboratory models, adopt a cellular state more similar to PDAC cells in tumors. Further, using the TIFM model we identified arginine biosynthesis as a metabolic adaptation PDAC cells engage to cope with microenvironmental arginine starvation driven by myeloid cells in PDAC tumors. Altogether, these data show that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity and enable the discovery of novel cancer metabolic phenotypes.
Institute:University of Chicago
Last Name:Apiz Saab
First Name:Juan
Address:929 E. 57th St.
Email:japizsaab@uchicago.edu
Phone:7738346506

Subject:

Subject ID:SU002629
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 type Condition
SA254631A35097-120Plasma Arg1fl/fl
SA254632A35097-0Plasma Arg1fl/fl
SA254633A35096-120Plasma Arg1fl/fl
SA254634A35097-240Plasma Arg1fl/fl
SA254635A35096-240Plasma Arg1fl/fl
SA254636A35098-0Plasma Arg1fl/fl
SA254637A35098-30Plasma Arg1fl/fl
SA254638A35098-240Plasma Arg1fl/fl
SA254639A35098-120Plasma Arg1fl/fl
SA254640A35096-0Plasma Arg1fl/fl
SA254641A35097-30Plasma Arg1fl/fl
SA254642A35096-30Plasma Arg1fl/fl
SA2546430789-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546440785-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254645A35465-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546460787-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546470787-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546480787-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546490787-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254650A35465-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254651A35465-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254652A35469-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546530785-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254654A35469-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254655A35469-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254656A35465-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254657A35469-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546580788-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546590785-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254660A35066-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254661A35066-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254662A35066-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546630788-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546640789-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546650789-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254666A35089-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254667A35066-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546680788-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254669A35089-120Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546700788-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546710785-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA2546720789-0Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254673A35089-240Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254674A35089-30Plasma Lyz2-Cre+/+; Arg1fl/fl
SA254675A35098_tumor_ControlTumor Arg1fl/fl
SA254676A35097_tumor_ControlTumor Arg1fl/fl
SA254677A35096_tumor_ControlTumor Arg1fl/fl
SA254678A35466_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA254679A35469_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA254680A35465_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA2546810788_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA2546820785_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA2546830787_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA2546840789_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
SA254685A35089_tumor_Arg1_KOTumor Lyz2-Cre+/+; Arg1fl/fl
Showing results 1 to 55 of 55

Collection:

Collection ID:CO002622
Collection Summary:6~8-month-old female & male Lyz2-Cre +/+; Arg1fl/fl and litter mate control Arg1fl/fl mice with murine PDAC orthotopic tumors underwent dual jugular vein & carotid artery catheterization surgery. On day 5 of post recovery, mice received a 0.28 mg/g 10 min. bolus followed by a continuous 4 hr. infusion 0.005 mg/g/min infusion of 15N2-glutamine (Cambridge Isotope Laboratory #NLM-1328-PK). Plasma samples were taken at time points: 0' 15' 30' 60' 120' 180’ 240’. Tumors and tissues were harvested at 240’ and immediately snap frozen with liquid nitrogen stored at -80°C prior to analysis.
Sample Type:Tumor, plasma

Treatment:

Treatment ID:TR002641
Treatment Summary:6~8-month-old female & male Lyz2-Cre +/+; Arg1fl/fl and litter mate control Arg1fl/fl mice with murine PDAC orthotopic tumors underwent dual jugular vein & carotid artery catheterization surgery. On day 5 of post recovery, mice received a 0.28 mg/g 10 min. bolus followed by a continuous 4 hr. infusion 0.005 mg/g/min infusion of 15N2-glutamine (Cambridge Isotope Laboratory #NLM-1328-PK). Plasma samples were taken at time points: 0' 15' 30' 60' 120' 180’ 240’. Tumors and tissues were harvested at 240’ and immediately snap frozen with liquid nitrogen stored at -80°C prior to analysis.

Sample Preparation:

Sampleprep ID:SP002635
Sampleprep Summary:Cryogenically frozen tumor pieces were ground to a fine homogenous powder with a liquid nitrogen cooled mortar and pestle. ~30mg of tissue powder was weighed into sample tubes, and metabolites were extracted with 600µL HPLC grade methanol, 300µL HPLC grade water, and 400µL chloroform. Samples were vortexed for 10min at 4°C, centrifuged 21,000xg at 4°C for 10 min. 400µL of the aqueous top layer was removed into a new tube and dried under nitrogen. Dried tumor extracts were resuspended in 100µL HPLC grade water and LC-MS analysis was performed as described before(Sullivan et al., 2019b, 2019a). For plasma samples, we extracted polar metabolites from 5µL of sample using 45µL of a 75:25:0.1 HPLC grade acetonitrile:methanol:formic acid extraction mix. Samples in extraction mix were vortexed for 10 min at 4°C and centrifugated at 15,000x rpm for 10 min at 4°C to pellet insoluble material. 20µL of the soluble polar metabolite supernatant was moved to sample vials for analysis by LC-MS.

Combined analysis:

Analysis ID AN004163
Analysis type MS
Chromatography type HILIC
Chromatography system Thermo Vanquish
Column Waters Atlantis BEH Z-HILIC (150 x 2.1 mm, 2.5um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Orbitrap IQ-X Tribrid
Ion Mode UNSPECIFIED
Units Natural abundance corrected percentages

Chromatography:

Chromatography ID:CH003082
Instrument Name:Thermo Vanquish
Column Name:Waters Atlantis BEH Z-HILIC (150 x 2.1 mm, 2.5um)
Column Temperature:30°C
Flow Gradient:0 minute: 85% B, 0.5 minute: 85% B, 18 minutes: 20% B, 20 minutes: 20% B, 20.5 minutes: 85% B and 28 minutes: 85% B
Flow Rate:0.2 mL/minute
Solvent A:20 mM ammonium bicarbonate at pH 9.6, adjusted by ammonium hydroxide addition
Solvent B:100% Acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS003910
Analysis ID:AN004163
Instrument Name:Thermo Orbitrap IQ-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Data acquisition was done using the Xcalibur software (Thermo Scientific) in full-scan mode with a range of 70-1000 m/z at 60K. Metabolite identification was done by matching the retention time and MS/MS fragmentation to the reference standards. Data analysis was performed using Tracefinder 5.1 software (Thermo Scientific).
Ion Mode:UNSPECIFIED
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