Summary of Study ST002935
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 PR001826. The data can be accessed directly via it's Project DOI: 10.21228/M8PH9P 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 | ST002935 |
| Study Title | Title: Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth |
| Study Type | PBMC vs Tumor CD163+ |
| Study Summary | Glioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and human GBM patients identified the de-novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing the creatine transporter (SLC6A8). Therefore, we hypothesized that TAMCs provide creatine to tumors, promoting GBM progression. Isotopic tracing demonstrated that TAMC-secreted creatine can be taken up by tumor cells. Creatine supplementation protected tumors from hypoxia-induced stress which was abrogated with genetic ablation or pharmacologic inhibition of SLC6A8. Lastly, inhibition of creatine transport using the clinically relevant compound, RGX-202-01, blunted tumor growth, and enhanced radiation therapy in-vivo. This work highlights that myeloid-to-tumor transfer of creatine promotes tumor growth in the hypoxic niche. |
| Institute | Northwestern University, Feinberg School of Medicine |
| Department | Neurological Surgery |
| Laboratory | Jason Miska |
| Last Name | Miska |
| First Name | Jason |
| Address | 676 N St. Clair |
| jason.miska@northwestern.edu | |
| Phone | 8478678201 |
| Submit Date | 2023-10-16 |
| Num Groups | 2 |
| Total Subjects | 5 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-11-03 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP003054 |
| Sampleprep Summary: | Isolated TAMC samples were dried using a SpeedVac. Acetonitrile (50%) was added to the tube for reconstitution following overtaxing for 30 s. Sample solution was then centrifuged for 15 min at 20,000g and 4°C. Supernatant was collected for LC-MS analysis. |
