Fig 2: S1P exacerbates the pro-inflammatory milieu by inducing pro-inflammatory cytokine release from lung cancer-derived PBMCs in a S1PR3-dependent manner. The activation of S1PR3 by the exogenous S1P enhances its own production and fosters the release of TNF-a in a SPHK I-dependent manner (black arrows), and of IL-6 via SPHK I/II (red arrows); S1P-induced IL-6, but not TNF-a, release from PBMCs of lung cancer patients is mTOR- and K-Ras-dependent (red arrows).

Fig 3: S1PR3 expression in lung tissues of ADK and SCC patients. Western blotting analysis showed that female (A) and male (D) ADK patients had higher levels of S1PR3 (55 kDa) in cancerous tissue (cancer, female n = 8; male n = 11) compared to the respective non-cancerous tissues (non-cancer, female n = 4; male n = 7). S1PR3 expression was similar in non-cancerous (non-cancer, female n = 4; male n = 6) and cancerous (cancer, female n = 4; male n = 12) tissues of SCC patients, regardless of sex (B,E). S1PR3 detection was performed on the same blot when evaluating ADK or SCC patients. Representative blot of S1PR3 expression in non-cancerous (NC) and cancerous (C) tissues of female (C) and male (F) ADK and SCC patients. HSC70 (70 kDa) was used as the loading control. A quantitative analysis was performed using ImageJ software (1.53a http://imagej.nih.gov/ij, accessed on 1 October 2022, NIH, Bethesda, MD, USA). Data are represented as scatter dot plots indicating the median. Statistical differences were assessed by means of a two-tailed Mann–Whitney U test. S1PR3: sphingosine-1-phosphate receptor 3; HSC70: Heat shock cognate protein 70; ADK: lung adenocarcinoma; SCC: lung squamous cell carcinoma.