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.

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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 IDST002935
Study TitleTitle: Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth
Study TypePBMC vs Tumor CD163+
Study SummaryGlioblastoma (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
DepartmentNeurological Surgery
LaboratoryJason Miska
Last NameMiska
First NameJason
Address676 N St. Clair
Emailjason.miska@northwestern.edu
Phone8478678201
Submit Date2023-10-16
Num Groups2
Total Subjects5
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-11-03
Release Version1
Jason Miska Jason Miska
https://dx.doi.org/10.21228/M8PH9P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

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

mb_sample_id local_sample_id Treatment
SA318402Les-Jas-20190812-13PBMC
SA318403Les-Jas-20200214-04PBMC
SA318404Les-Jas-20190812-14PBMC
SA318405Les-Jas-20190812-15PBMC
SA318406Les-Jas-20200214-03PBMC
SA318407Les-Jas-20200214-02Tumor
SA318408Les-Jas-20190812-18Tumor
SA318409Les-Jas-20190812-16Tumor
SA318410Les-Jas-20190812-17Tumor
SA318411Les-Jas-20200214-01Tumor
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