Objective: Recent studies showed that the S100A4 is candidate prognostic marker or therapeutic targets in cancers. In this study, we first evaluate the expression of S100A4 mRNA in Wilms tumor (WT) and its relationship to the clinicopathological parameters and prognosis. We then tested a hypothesis that the S100A4 gene plays a role in cell proliferation, apoptosis, invasiveness and capillary network formation and regression of established orthotopic tumors of human WT cells.
Materials and methods: Expression of V S100A4 mRNA was examined in 48 surgical specimens of WTs by Quatitive Reverse transcription-PCR analysis (Q-PCR). Correlation between the expression of S100A4 mRNA and clinicopathological parameters was analyzed. We used in vitro and vivo experiments with RNA interference to evaluate the functional role of S100A4 and its potential as a therapeutic target for WT.
Results: S100A4 mRNA levels were significantly higher in carcinoma specimens than in non neoplastic tissues. S100A4 mRNA expression was significantly correlated with tumor size, vascular invasion, node metastasis and tumor stage. We observed that shRNA-mediated suppression of the S100A4 gene significantly promoted apoptosis and reduced the proliferative and invasive capability, angiogenesis of the WT cells SK-NEP-1 in vitro. S100A4-shRNA-transfected cells exhibited a reduced rate of tumor growth under in vivo conditions. Microvascular density (MVD) was reduced by 62% due to S100A4-shRNA treatment (p < 0.01).
Conclusions: Our present results suggest that S100A4 mRNA plays an important role in the development of WT. It might be useful in evaluating the outcome of patients with WT. S100A4 may be a promising therapeutic target for WT.