Toll-like receptor 3 expression inhibits cell invasion and migration and predicts a favorable prognosis in neuroblastoma

• Positive TLR3 expression was associated with favorable histology and prognosis in neuroblastoma.
• Activation of TLR3 by agonist polyinosinic:polycytidylic acid [poly(I:C)] is effective to suppress cell migration and invasion.
• Poly(I:C) may decrease organized assembly of F-actin and filopodia formation, in TLR3-expressing SK-N-AS cells.
• Poly(I:C) promotes GAP-43 expression, a marker of neuronal differentiation, in SK-N-AS cells.
• The above effects of poly(I:C) on SK-N-AS neuroblastoma cells could be reversed by TLR3-targeting siRNA treatment.

To evaluate the clinical significance of TLR3 expression on neuroblastomas, we performed immunohistochemical study on archival tissues and in vitro studies on neuroblastoma cell lines. The results showed that positive TLR3 expression was associated with favorable histology and prognosis. Activation of TLR3 by polyinosinic:polycytidylic acid [poly(I:C)] treatment is effective to suppress cell migration and invasion and to decrease organized assembly of F-actin and filopodia formation, in TLR3-expressing SK-N-AS cells, which could be reversed by TLR3-targeting siRNA treatment. TLR3 agonist poly(I:C) promotes GAP-43 expression also in SK-N-AS cells only. Taken together, TLR3 could serve to predict favorable behavior in neuroblastomas.