Summary of Study ST003143

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 PR001954. The data can be accessed directly via it's Project DOI: 10.21228/M84X6Q 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 IDST003143
Study TitleMitochondrial complex I promotes kidney cancer metastasis
Study SummaryMost kidney cancers display metabolic dysfunction but how this relates to cancer progression in humans is unknown. We infused 13C-labeled nutrients during surgical tumour resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic cultures ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with measurements of respiration in mitochondria isolated from kidneys and tumours, reveal electron transport chain (ETC) defects in ccRCC. However, ccRCC metastases unexpectedly have enhanced TCA cycle labeling compared to primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, while inhibiting ETC complex I decreases metastasis. These findings indicate that metabolic properties and liabilities evolve during kidney cancer progression in humans, and that mitochondrial function is limiting for metastasis but not for growth at the original site.
Institute
University of Texas Southwestern Medical Center at Dallas
Last NameBezwada
First NameDivya
Address5323 Harry Hines Boulevard, Dallas, TX 75390-8502
Emaildbezwada@scripps.edu
Phone214-648-2587
Submit Date2023-12-14
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2024-06-17
Release Version1
Divya Bezwada Divya Bezwada
https://dx.doi.org/10.21228/M84X6Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001954
Project DOI:doi: 10.21228/M84X6Q
Project Title:Mitochondrial complex I promotes kidney cancer metastasis
Project Summary:Most kidney cancers display metabolic dysfunction but how this relates to cancer progression in humans is unknown. We infused 13C-labeled nutrients during surgical tumour resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic cultures ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with measurements of respiration in mitochondria isolated from kidneys and tumours, reveal electron transport chain (ETC) defects in ccRCC. However, ccRCC metastases unexpectedly have enhanced TCA cycle labeling compared to primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, while inhibiting ETC complex I decreases metastasis. These findings indicate that metabolic properties and liabilities evolve during kidney cancer progression in humans, and that mitochondrial function is limiting for metastasis but not for growth at the original site.
Institute:University of Texas Southwestern Medical Center at Dallas
Laboratory:Ralph DeBerardinis, MD, PhD
Last Name:Bezwada
First Name:Divya
Address:5323 Harry Hines Boulevard, Dallas, TX 75390-8502
Email:dbezwada@scripps.edu
Phone:214.648-2587

Subject:

Subject ID:SU003260
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female
Species Group:Mammals

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Diagnosis
SA340628VM23_Adjacent_KidneyAdjacent_Kidney -
SA340629VM17_Adjacent_KidneyAdjacent_Kidney -
SA340630VM39_Adjacent_KidneyAdjacent_Kidney -
SA340631VM54_Adjacent_KidneyAdjacent_Kidney -
SA340632VM59_Adjacent_KidneyAdjacent_Kidney -
SA340633VM13_Adjacent_KidneyAdjacent_Kidney -
SA340634VM10_Adjacent_KidneyAdjacent_Kidney -
SA340635VM32_Adjacent_KidneyAdjacent_Kidney -
SA340636VM66_Adjacent_KidneyAdjacent_Kidney -
SA340637VM35_Adjacent_KidneyAdjacent_Kidney -
SA340638VM49_Adjacent_KidneyAdjacent_Kidney -
SA340639VM25_Adjacent_KidneyAdjacent_Kidney -
SA340640VM40_Adjacent_KidneyAdjacent_Kidney -
SA340641VM41_Adjacent_KidneyAdjacent_Kidney -
SA340642VM36_Adjacent_KidneyAdjacent_Kidney -
SA340643VM26_Adjacent_KidneyAdjacent_Kidney -
SA340644VM53_Adjacent_KidneyAdjacent_Kidney -
SA340645VM58_Adjacent_KidneyAdjacent_Kidney -
SA340646VM50_Adjacent_KidneyAdjacent_Kidney -
SA340647VM67_Adjacent_KidneyAdjacent_Kidney -
SA340648VM65_Adjacent_KidneyAdjacent_Kidney -
SA340649VM63_Adjacent_KidneyAdjacent_Kidney -
SA340650VM38_Adjacent_KidneyAdjacent_Kidney -
SA340651VM47_Adjacent_KidneyAdjacent_Kidney -
SA340652VM60_Adjacent_KidneyAdjacent_Kidney -
SA340653VM39_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340654VM23_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340655VM09_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340656VM25_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340657VM17_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340658VM53_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340659VM47_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340660VM66_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340661VM35_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340662VM38_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340663VM49_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340664VM10_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340665VM13_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340666VM40_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340667VM41_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340668VM46_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340669VM21_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340670VM67_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340671VM26_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340672VM32_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340673VM58_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340674VM34_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340675VM36_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340676VM60_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340677VM50_Primary_Tumour_CCRCCPrimary_Tumour CCRCC
SA340678VM30_Primary_Tumour_CHROMOPHOBEPrimary_Tumour CHROMOPHOBE
SA340679VM31_Primary_Tumour_ONCOCYTOMAPrimary_Tumour ONCOCYTOMA
SA340680VM11_Primary_Tumour_ONCOCYTOMAPrimary_Tumour ONCOCYTOMA
SA340681VM59_Primary_Tumour_ONCOCYTOMAPrimary_Tumour ONCOCYTOMA
SA340682VM63_Primary_Tumour_PAPILLARYPrimary_Tumour PAPILLARY
SA340683VM44_Primary_Tumour_PAPILLARYPrimary_Tumour PAPILLARY
SA340684VM65_Primary_Tumour_PAPILLARYPrimary_Tumour PAPILLARY
SA340685VM14_Primary_Tumour_PAPILLARYPrimary_Tumour PAPILLARY
SA340686VM12_Primary_Tumour_PAPILLARYPrimary_Tumour PAPILLARY
Showing results 1 to 59 of 59

Collection:

Collection ID:CO003253
Collection Summary:Human tissues were collected under clinical trials approved and monitored by the Institutional Review Board (IRB) at the University of Texas Southwestern Medical Center. Tissues were collected after surgery, flash frozen in liquid nitrogen, and stored in a -80 freezer.
Sample Type:Tissue
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003269
Treatment Summary:Not applicable.

Sample Preparation:

Sampleprep ID:SP003267
Sampleprep Summary:Frozen tissue fragments weighing 10-30mg were added to ice cold 80:20 methanol:water and extracted for metabolomics analysis. Samples were subjected to three freeze-thaw cycles, then centrifuged at 16,000xg for 20 minutes to precipitate macromolecules. The supernatant was evaporated using a vacuum concentrator. Samples were resuspended in 100 μL of 0.1% formic acid in water, vortexed for 30 seconds, and centrifuged at 16,000g for 15 minutes. Supernatant was transferred to an autosampler vial and then run on the MS.

Chromatography:

Chromatography ID:CH003904
Instrument Name:Agilent 6550
Column Name:Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
Column Temperature:25
Flow Gradient:0 min: 1% B; 5 min: 5% B; 15 min: 99%; 23 min: 99%; 24 min: 1%; 25 min: 1%
Flow Rate:250 μL min-1
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN005157
Analysis Type:MS
Chromatography ID:CH003904
Num Factors:5
Num Metabolites:384
Units:Normalized Abundance
  
Analysis ID:AN005158
Analysis Type:MS
Chromatography ID:CH003904
Num Factors:5
Num Metabolites:384
Units:Normalized Abundance
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