Expression of matrix metalloproteinases and the metastasis-associated geneS100A4 in human neuroblastoma and primitive neuroectodermal tumor cells

Background: Matrix metalloproteinases (MMPs) and their endogenous inhibitor s (tissue inhibitors of MMPs; TIMPs) have been shown to correlate with in v itro invasiveness and clinical outcome in several adult malignancies. The i mportance of MMP and TIMP expression in neuroblastoma (NB) and primitive ne uroectodermal tumors (PNET) is incompletly understood. The aim of the curre nt study was to relate in vitro invasion of NE and PNET cell lines with MMP and TIMP expression and evaluate the effect of a synthetic MMP inhibitor. Furthermore, S100A4 levels were determined because recent reports have sugg ested a possible associaton between MMPs, TIMPs, and the metastasis-associa ted gene S100A4. Methods: Expression of MMPs, TIMPs, and S100A4 was evaluated at both mRNA a nd protein levels in 2 human NE and 2 PNET cell lines. In vitro invasion an d effects of the synthetic MMP inhibitor Marimastat were assessed in the Tr answell chamber assay. Results: The most invasive cells expressed the highest levels of MMPs and S 100A4. Marimastat reduced invasion by 30%. Conclusions: In vitro invasion correlated with MMP and S100A4 expression. T he fact that Marimastat reduced in vitro invasion is encouraging for furthe r studies on a possible therapeutic application for proteinase inhibitors. Copyright (C) 2001 by W.B. Saunders Company.