Summary of project PR002203
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 PR002203. The data can be accessed directly via it's Project DOI: 10.21228/M8VN7V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002203 |
| Project DOI: | doi: 10.21228/M8VN7V |
| Project Title: | Dietary fructose enhances tumor growth indirectly via interorgan lipid transfer |
| Project Summary: | Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup (HFCS) as a sweetener. It has been proposed that fructose promotes the growth of some tumors by serving as a direct fuel. Here, we show that fructose supplementation enhances tumor growth in animal models of melanoma, breast cancer, and cervical cancer without causing weight gain or insulin resistance. Interestingly, the cancer cells themselves were unable to use fructose readily as a nutrient because they did not express ketohexokinase-C (KHK-C). Primary hepatocytes did express KHK-C, resulting in fructolysis and the excretion of a variety of lipid species, including lysophosphatidylcholines (LPCs). In co-culture experiments, hepatocyte-derived LPCs were consumed by cancer cells and used to generate phosphatidylcholines (PCs), the major phospholipid of cell membranes. In vivo, HFCS supplementation increased several LPC species by >7-fold in serum. Administration of LPCs to mice was sufficient to increase tumor growth. Pharmacological inhibition of ketohexokinase had no direct effect on cancer cells, but it decreased circulating LPC levels and prevented fructose-mediated tumor growth in vivo. These findings reveal that fructose supplementation increases circulating nutrients such as LPCs, which can enhance tumor growth through a cell non-autonomous mechanism. |
| Institute: | Washington University in St. Louis |
| Department: | Chemistry |
| Laboratory: | Gary Patti |
| Last Name: | Fowle-Grider |
| First Name: | Ronald |
| Address: | 6101 Washington Blvd Unit 202, SAINT LOUIS, MO, 63112, USA |
| Email: | rjfowle@wustl.edu |
| Phone: | 309-265-7545 |
Summary of all studies in project PR002203
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003570 | Hepatocytes transform fructose into polar metabolites that are selectively utilized by cancer cells | Human (Homo sapiens), Mouse (Mus musculus) | Washington University in St. Louis | MS | 2025-03-17 | 1 | 6 | Uploaded data (148M)* |
| ST003571 | Hepatocytes transform fructose into lipids that can metabolized by cancer cells | Human (Homo sapiens), Mouse (Mus musculus) | Washington University in St. Louis | MS | 2024-11-27 | 1 | 13 | Uploaded data (35M)* |
| ST003572 | Dietary sugar supplementation in mice enhances the availability of many circulating lipids including lysophosphatidylcholines | Mus musculus | Washington University in St. Louis | MS | 2024-11-27 | 1 | 19 | Uploaded data (76.3M)* |
