Home
Resources
Publications
Itaconic Acid Mediates Crosstalk Between Macrophage Metabolism and Peritoneal Tumors

Itaconic Acid Mediates Crosstalk Between Macrophage Metabolism and Peritoneal Tumors

Jonathan M Weiss, Luke C Davies, Megan Karwan, Lilia Ileva, Michelle K Ozaki, Robert Ys Cheng, Lisa A Ridnour, Christina M Annunziata, David A Wink, Daniel W McVicar

J Clin Invest. 2018 Aug 31;128(9):3794-3805.

PMID: 29920191

Abstract:

Control of cellular metabolism is critical for efficient cell function, although little is known about the interplay between cell subset-specific metabolites in situ, especially in the tumor setting. Here, we determined how a macrophage-specific (Mϕ-specific) metabolite, itaconic acid, can regulate tumor progression in the peritoneum. We show that peritoneal tumors (B16 melanoma or ID8 ovarian carcinoma) elicited a fatty acid oxidation-mediated increase in oxidative phosphorylation (OXPHOS) and glycolysis in peritoneal tissue-resident macrophages (pResMϕ). Unbiased metabolomics identified itaconic acid, the product of immune-responsive gene 1-mediated (Irg1-mediated) catabolism of mitochondrial cis-aconitate, among the most highly upregulated metabolites in pResMϕ of tumor-bearing mice. Administration of lentivirally encoded Irg1 shRNA significantly reduced peritoneal tumors. This resulted in reductions in OXPHOS and OXPHOS-driven production of ROS in pResMϕ and ROS-mediated MAPK activation in tumor cells. Our findings demonstrate that tumors profoundly alter pResMϕ metabolism, leading to the production of itaconic acid, which potentiates tumor growth. Monocytes isolated from ovarian carcinoma patients' ascites fluid expressed significantly elevated levels of IRG1. Therefore, IRG1 in pResMϕ represents a potential therapeutic target for peritoneal tumors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP97654	Itaconic acid		97-65-4	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: