Role of serum E-selectin (ELAM-1) and inflammatory parameters in patients with renal cell carcinoma

Abstract

(BACKGROUND). E-selectin is an adhesion molecule expressed on IL-1 activated endothelial cells and it binds to carbohydrate ligands such as sialy Lewis A antigen (SLeA) or Lewis X antigen (SLeX) on cancer cells. This mechanism is supposed to play an important role during hematogenous metastasis. Some of renal cell carcinomas (RCC) are known to produce inflammatory cytokines such as IL-1 beta and IL-6 and clinical evidence shows that the prognosis of this type of tumor is generally poor. We investigated whether this adhesion molecule was involved in hematogenous metastasis. (METHOD). In the present study, soluble E-selectin level was measured in the sera of 89 patients with RCC prior to nephrectomy or IFN treatment using sanwich ELISA method. (RESULTS). The results indicated that high E-selectin concentration in the patients' sera was correlated with low incidence of metastasis and consequently correlated with good prognosis of RCC patients. Inflammatory serum parameters, such as serum C reactive protein (CRP), immunosuppressive acid protein (IAP) and erythrocyte sediment rate (ESR) were also assessed and these parameters were revealed to be negatively correlated with the serum level of E-selectin. In order to investigate this mechanism, we performed in vitro study on RCC cell/endothelial cell adhesion. IL-1 beta enhanced adhesion of 2 RCC cell lines and this adhesion was partially inhibited by adding exogenous E-selectin into the culture medium. Expression of SLeA and SLeX were demonstrated on the cell surface of 2 RCC cell lines by flowcytometric analysis. (CONCLUSION). The results suggested that E-selectin and SLeX/SLeA interaction was involved in the adhesion between RCC and endothelial cells and also inflammatory cytokine production by RCC cells was a risk factor for metastasis through E-selectin induction. Although expression of E-selectin on endothelial cells facilitates metastasis, excessive production of E-selectin into the serum was suggested to have inhibitory effect against metastasis.