Sphingosine 1-phosphate derived from tumor-educated hepatic stellate cells combining with S1PR4 promotes tumor associated macrophages differentiation through FAO modulation
Feng R., Cui Z., Yang L., Liu Z.
Animal Study, published in Sci Rep (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Sci Rep (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40592997
- PMCID
- PMC12218931
- DOI
- 10.1038/s41598-025-02588-6
- Citations
- 2
Abstract (original English)
The tumor immune microenvironment (TIME) is significance to the occurrence and development of tumors. Macrophages, making great contributes to TIME, develop into tumor-associated macrophages (TAM) under the influence of the tumor microenvironment (TME), resulting in altered metabolic pathways. Sphingosine 1-phosphate (S1P) is involved in immune regulation as a lipid metabolite. The role of S1P in the differentiation and metabolic regulation of tumor-associated macrophages is unknown. Meanwhile, the source of S1P in TME is not very clear. Our research found that hepatic stellate cells co-cultured with tumor cells could prompt macrophages to the M2 phenotype of TAM differentiation. It was further discovered that S1P activated peroxisome proliferator-activated receptor α (PPARα) by binding to S1P receptor 4 (S1PR4) of macrophages, upregulating lipid metabolism and inducing the TAM differentiation. Ultimately, tumor cells activated nuclear factor erythroid 2-related factor 2 (Nrf2) in hepatic stellate cells (HSCs), enhancing sphingosine kinase 1 (SphK1) expression and elevating S1P production and secretion. This study has demonstrated a possible interaction pathway among tumor cells, HSCs and macrophages. It has revealed that tumor cells activate the Nrf2/SphK1 pathway in HSCs to secrete S1P, which subsequently bound S1PR4, triggered PPARα activation, and drove macrophage polarizat
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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