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S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.
- Source :
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Journal of Experimental & Clinical Cancer Research (17569966) . 1/5/2023, Vol. 42 Issue 1, p1-17. 17p. - Publication Year :
- 2023
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Abstract
- Background: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. Methods: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. Results: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. Conclusion: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis. Highlights: • Obesity negatively impacted progression-free survival and overall survival in lymphoma patients while an aggressive tumor growth pattern was found in obesity-lymphoma mice. • S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth in obesity-lymphoma. • S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. • S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SPHINGOSINE kinase
*SIGNALS & signaling
*TISSUE arrays
*TUMOR microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 42
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Experimental & Clinical Cancer Research (17569966)
- Publication Type :
- Academic Journal
- Accession number :
- 161137105
- Full Text :
- https://doi.org/10.1186/s13046-022-02589-7