Inhibition of Microsomal Prostaglandin E Synthase-1 in Cancer-Associated Fibroblasts Suppresses Neuroblastoma Tumor Growth.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29804818.
- Also identified by DOI 10.1016/j.ebiom.2018.05.008 and PMC identifier 6021299.
- Licence recorded as CC BY-NC-ND.
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Abstract
Despite recent progress in diagnosis and treatment, survival for children with high-risk metastatic neuroblastoma is still poor. Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>)-driven inflammation promotes tumor growth, immune suppression, angiogenesis and resistance to established cancer therapies. In neuroblastoma, cancer-associated fibroblasts (CAFs) residing in the tumor microenvironment are the primary source of PGE<sub>2</sub>. However, clinical targeting of PGE<sub>2</sub> with current non-steroidal anti-inflammatory drugs or cyclooxygenase inhibitors has been limited due to risk of adverse side effects. By specifically targeting microsomal prostaglandin E synthase-1 (mPGES-1) activity with a small molecule inhibitor we could block CAF-derived PGE<sub>2</sub> production leading to reduced tumor growth, impaired angiogenesis, inhibited CAF migration and infiltration, reduced tumor cell proliferation and a favorable shift in the M1/M2 macrophage ratio. In this study, we provide proof-of-principle of the benefits of targeting mPGES-1 in neuroblastoma, applicable to a wide variety of tumors. This non-toxic single drug treatment targeting infiltrating stromal cells opens up for combination treatment options with established cancer therapies.
Medical subject headings
- Inflammation
- Neovascularization, Pathologic
- Neuroblastoma
- Prostaglandin-E Synthases