Expression of matrix metalloproteinases and the metastasis-associated gene S100A4 in human neuroblastoma and primitive neuroectodermal tumor cells.
BACKGROUND
Matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of MMPs; TIMPs) have been shown to correlate with in vitro invasiveness and clinical outcome in several adult malignancies. The importance of MMP and TIMP expression in neuroblastoma (NB) and primitive neuroectodermal tumors (PNET) is incompletely understood. The aim of the current study was to relate in vitro invasion of NB 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 suggested a possible association between MMPs, TIMPs, and the metastasis-associated gene S100A4.


METHODS
Expression of MMPs, TIMPs, and S100A4 was evaluated at both mRNA and protein levels in 2 human NB and 2 PNET cell lines. In vitro invasion and effects of the synthetic MMP inhibitor Marimastat were assessed in the Transwell chamber assay.


RESULTS
The most invasive cells expressed the highest levels of MMPs and S100A4. Marimastat reduced invasion by 30%.


CONCLUSIONS
In vitro invasion correlated with MMP and S100A4 expression. The fact that Marimastat reduced in vitro invasion is encouraging for further studies on a possible therapeutic application for proteinase inhibitors.
Bjørnland
K
K
Institute for Surgical Research and the Department of Pediatric Surgery, The National Hospital, Oslo, Norway.
Bratland A
Rugnes
E
E
Pettersen
S
S
Johansen
H T
HT
Aasen
A O
AO
Fodstad
Ø
Ø
Ree
A H
AH
Maelandsmo
G M
GM
D015152:Blotting, Northern; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009447:Neuroblastoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology
D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D019714:Tissue Inhibitor of Metalloproteinases; C077591:S100A4 protein, human; D020782:Matrix Metalloproteinases