Summary of Study ST003898
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 PR002439. The data can be accessed directly via it's Project DOI: 10.21228/M8CG2W 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 | ST003898 |
| Study Title | Glycosaminoglycan-mediated lipoprotein uptake protects cancer cells from ferroptosis |
| Study Summary | Lipids are essential components of cancer cells due to their structural and signaling roles and many cancers take up extracellular lipids to meet metabolic demands. How these lipids contribute to cancer growth and progression remains poorly understood. Using functional genetic screens, lipoprotein uptake—the primary mechanism for lipid transport in circulation—is identify as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across numerous cancer types, an effect largely driven by lipoprotein delivery of α-tocopherol. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Disrupting GAG biosynthesis or acutely degrading surface GAGs reduces lipoprotein uptake, sensitizes cancer cells to ferroptosis, and impairs tumor growth in mice. Notably, human clear cell renal cell carcinomas (ccRCC), a lipid-rich malignancy, exhibit elevated levels of chondroitin sulfate and increased lipoprotein-derived α-tocopherol compared to normal kidney tissue. Altogether, this work establishes lipoprotein uptake as a critical anti-ferroptotic mechanism in cancer and implicates GAG biosynthesis as a therapeutic target. |
| Institute | University of Texas Southwestern Medical Center at Dallas |
| Department | Children's Research Institute |
| Laboratory | Metabolomics Facility |
| Last Name | Cai |
| First Name | Feng |
| Address | 6000 Harry Hines Blvd. |
| feng.cai@utsouthwestern.edu | |
| Phone | 2146483056 |
| Submit Date | 2025-04-24 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-05-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002439 |
| Project DOI: | doi: 10.21228/M8CG2W |
| Project Title: | Measuring α-tocopherol and cholesterol from ccRCC tissues |
| Project Summary: | Lipids are essential components of cancer cells due to their structural and signaling roles. To meet metabolic demands, many cancers take up extracellular lipids; however, how these lipids contribute to cancer growth and progression remains poorly understood. Here, using functional genetic screens, we identify lipoprotein uptake—the primary mechanism for lipid transport in circulation—as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across numerous cancer types, an effect largely driven by lipoprotein delivery of α-tocopherol, the most abundant form of vitamin E. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Disrupting GAG biosynthesis or acutely degrading surface GAGs reduces lipoprotein uptake, sensitizes cancer cells to ferroptosis, and impairs tumour growth in mice. Notably, human clear cell renal cell carcinomas (ccRCC), a lipid-rich malignancy, exhibit elevated levels of chondroitin sulfate and increased lipoprotein-derived α-tocopherol compared to normal kidney tissue. Altogether, our work establishes lipoprotein uptake as a critical anti-ferroptotic mechanism in cancer and implicates GAG biosynthesis as a therapeutic target. |
| Institute: | University of Texas Southwestern Medical Center at Dallas |
| Department: | Children's Research Institute |
| Laboratory: | Metabolomics Facility |
| Last Name: | Cai |
| First Name: | Feng |
| Address: | 6000 Harry Hines Blvd. |
| Email: | feng.cai@utsouthwestern.edu |
| Phone: | 2146483056 |
Subject:
| Subject ID: | SU004033 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Sample Information |
|---|---|---|---|
| SA429538 | 9456 (9) | Human patient ccRCC tissues | VM100_Adjacent Kidney |
| SA429539 | 9456 (10) | Human patient ccRCC tissues | VM100_Primary ccRCC |
| SA429540 | 9456 (11) | Human patient ccRCC tissues | VM101_Adjacent Kidney |
| SA429541 | 9456 (12) | Human patient ccRCC tissues | VM101_Primary ccRCC |
| SA429542 | 9456 (13) | Human patient ccRCC tissues | VM102_Adjacent Kidney |
| SA429543 | 9456 (14) | Human patient ccRCC tissues | VM102_Primary ccRCC |
| SA429544 | 9456 (15) | Human patient ccRCC tissues | VM103_Adjacent Kidney |
| SA429545 | 9456 (16) | Human patient ccRCC tissues | VM103_Primary ccRCC |
| SA429546 | 9456 (17) | Human patient ccRCC tissues | VM104_Adjacent Kidney |
| SA429547 | 9456 (18) | Human patient ccRCC tissues | VM104_Primary ccRCC |
| SA429548 | 9456 (19) | Human patient ccRCC tissues | VM105_Adjacent Kidney |
| SA429549 | 9456 (20) | Human patient ccRCC tissues | VM105_Primary ccRCC |
| SA429550 | 9456 (21) | Human patient ccRCC tissues | VM106_Adjacent Kidney |
| SA429551 | 9456 (22) | Human patient ccRCC tissues | VM106_Primary ccRCC |
| SA429552 | 9456 (23) | Human patient ccRCC tissues | VM107_Adjacent Kidney |
| SA429553 | 9456 (24) | Human patient ccRCC tissues | VM107_Primary ccRCC |
| SA429554 | 9456 (25) | Human patient ccRCC tissues | VM108_Adjacent Kidney |
| SA429555 | 9456 (26) | Human patient ccRCC tissues | VM108_Primary ccRCC |
| SA429556 | 9456 (27) | Human patient ccRCC tissues | VM109_Adjacent Kidney |
| SA429557 | 9456 (28) | Human patient ccRCC tissues | VM109_Primary ccRCC |
| SA429558 | 9456 (29) | Human patient ccRCC tissues | VM110_Adjacent Kidney |
| SA429559 | 9456 (30) | Human patient ccRCC tissues | VM110_Primary ccRCC |
| SA429560 | 9456 (31) | Human patient ccRCC tissues | VM111_Adjacent Kidney |
| SA429561 | 9456 (32) | Human patient ccRCC tissues | VM111_Primary ccRCC |
| SA429562 | 9456 (33) | Human patient ccRCC tissues | VM112_Adjacent Kidney |
| SA429563 | 9456 (34) | Human patient ccRCC tissues | VM112_Primary ccRCC |
| SA429564 | B4 (1) | Human patient ccRCC tissues | VM91_Adjacent Kidney |
| SA429565 | B4 (2) | Human patient ccRCC tissues | VM91_Primary ccRCC |
| SA429566 | B4 (3) | Human patient ccRCC tissues | VM92_Adjacent Kidney |
| SA429567 | B4 (4) | Human patient ccRCC tissues | VM92_Primary ccRCC |
| SA429568 | B4 (5) | Human patient ccRCC tissues | VM94_Adjacent Kidney |
| SA429569 | B4 (6) | Human patient ccRCC tissues | VM94_Primary ccRCC |
| SA429570 | 9456 (1) | Human patient ccRCC tissues | VM95_Adjacent Kidney |
| SA429571 | 9456 (2) | Human patient ccRCC tissues | VM95_Primary ccRCC |
| SA429572 | 9456 (3) | Human patient ccRCC tissues | VM96_Adjacent Kidney |
| SA429573 | 9456 (4) | Human patient ccRCC tissues | VM96_Primary ccRCC |
| SA429574 | 9456 (5) | Human patient ccRCC tissues | VM97_Adjacent Kidney |
| SA429575 | 9456 (6) | Human patient ccRCC tissues | VM97_Primary ccRCC |
| SA429576 | 9456 (7) | Human patient ccRCC tissues | VM98_Adjacent Kidney |
| SA429577 | 9456 (8) | Human patient ccRCC tissues | VM98_Primary ccRCC |
| Showing results 1 to 40 of 40 |
Collection:
| Collection ID: | CO004026 |
| Collection Summary: | We collected 50-100 mg of human ccRCC or adjacent kidney tissues, resuspended them in 800 µl of PBS, lysed using a BeadBlaster 24R (Benchmark Scientific) followed by sample sonication for 60 seconds. 1/10 of this solution was collected for protein quantification for normalization of values. The remaining supernatant was processed as following: addition of 700 µL of LC/MS grade ethanol (EtOH) + 2.1 mL of LC/MS grade hexane (Sigma). Solutions were then thoroughly vortexed for 5 minutes at 4°C. After centrifugation, the upper layer was collected into a new tube. Next, we re-extracted the remaining aqueous phase by adding 300 µL of EtOH + 900 µL of hexane, followed by vortexing and centrifugation. The two non-polar phases containing vitamin E and cholesterol were then collected together, dried down and stored at -70°C until analysis. |
| Sample Type: | Tumor tissue, Adjacent kidney tissue |
Treatment:
| Treatment ID: | TR004042 |
| Treatment Summary: | no treatment |
Sample Preparation:
| Sampleprep ID: | SP004039 |
| Sampleprep Summary: | Pellets are reconstituted into LC/MS grade ethanol (EtOH, 200 µl) and centrifuged at 21,000 G for 15 min, the supernatants are transferred into LC-MS vials for analysis. |
Combined analysis:
| Analysis ID | AN006401 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Shimadzu 20AD |
| Column | Phenomenex Synergi Polar-RP (150 x 2mm, 4um, 80Å) |
| MS Type | APCI |
| MS instrument type | Triple quadrupole |
| MS instrument name | ABI Sciex 5500 QTrap |
| Ion Mode | POSITIVE |
| Units | ion count |
Chromatography:
| Chromatography ID: | CH004853 |
| Instrument Name: | Shimadzu 20AD |
| Column Name: | Phenomenex Synergi Polar-RP (150 x 2mm, 4um, 80Å) |
| Column Temperature: | 40 |
| Flow Gradient: | 0–2.0 min, linear gradient 0–60% B, 2.0–5.6 min, linear gradient 60–100% B, then the column was washed with 100% B for 4.4 min before reconditioning it for 5 min using 0% B |
| Flow Rate: | 0.5mL/min |
| Solvent A: | 65% methanol/35% water; 2.0 mM ammonium acetate |
| Solvent B: | 63% methanol/37% isopropanol; 2.0 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS006102 |
| Analysis ID: | AN006401 |
| Instrument Name: | ABI Sciex 5500 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | APCI |
| MS Comments: | An AB SCIEX 5500 QTRAP liquid chromatography/mass spectrometer (Applied Biosystems SCIEX), equipped with a vacuum degasser, a quaternary pump, an autosampler, a thermostatted column compartment, and a triple quadrupole/ion-trap mass spectrometer with atmospheric pressure chemical ionization interface, controlled by AB SCIEX Analyst 1.6.1 Software. The MRMs (Q1/Q3) used for metabolites were 369.0/161.0 (cholesterol, CE: 15), 431/165 (α-tocopherol, CE: 30), and 437/171 (α-tocopherol-d6, internal standard, CE: 30). The Multiquant 3.0 software was used to identify peak and integration. |
| Ion Mode: | POSITIVE |
