S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma

被引：11
作者：
Wang, Xingtong [1 ,2 ]
Guo, Wei [1 ,2 ]
Shi, Xiaoju [1 ,3 ]
Chen, Yujia [1 ,4 ]
Yu, Youxi [1 ,3 ]
Du, Beibei [5 ]
Tan, Min [1 ]
Tong, Li [6 ]
Wang, Anna [2 ]
Yin, Xianying [2 ]
Guo, Jing [2 ]
Martin, Robert C. C. [1 ]
Bai, Ou [2 ]
Li, Yan [1 ]
机构：
[1] Univ Louisville, Sch Med, Dept Surg, 511 S Floyd ST MDR Bldg, Rm326A, Louisville, KY 40202 USA
[2] Jilin Univ, Canc Ctr, Dept Hematol, Hosp 1, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China
[3] Jilin Univ, Hosp 1, Dept Hepatobiliary & Pancreat Surg, Changchun 130021, Peoples R China
[4] Jilin Univ, Hosp 1, Dept Gastrointestinal Surg, Changchun 130021, Peoples R China
[5] Jilin Univ, China Japan Union Hosp, Dept Cardiol, Changchun 130033, Peoples R China
[6] Jilin Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Changchun 130021, Peoples R China
来源：
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2023年 / 42卷 / 01期
关键词：
Lymphoma; Free fatty acid; S1P; SPHK signaling; Tumor microenvironment; Obesity; SPHINGOSINE-1-PHOSPHATE RECEPTOR 1; SPHINGOSINE; 1-PHOSPHATE; CANCER-CELLS; EXPRESSION; MICROENVIRONMENT; INFLAMMATION; MECHANISMS; SUPPRESSOR; LEUKEMIA; TARGET;
D O I：
10.1186/s13046-022-02589-7
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：17
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