In the central nervous system, the secretion of interstitial collagenase and 65-kD type IV collagenase (gelatinase A) was observed in cultured fetal astrocytes and in glioma cell lines.4 The production of matrilysin and stromelysin is also reported in human glioma cell lines,37 and the production of gelatinase B is elevated in human malignant gliomas.42 In addition to TIMPs, human glioma cell lines secrete smaller inhibitors of metalloproteinases named IMP-1, IMP-2, and IMP-3,4 the first two of which are also detected in the conditioned medium of rabbit brain capillary endothelial cells.18 The inhibitor IMP-2 has been considered to be identical to TIMP-2, but the other two small inhibitors have not yet been characterized. Two myelin-derived proteins with molecular weights of 35 kD and 250 kD are also found to contain the MMP blocking sequence and are thought to be responsible for inhibiting the spread of TB16 melanoma cells and 3T3 fibroblasts in the central nervous system.9,40 In addition, the expressions of MMP and TIMP genes in tumors are known to be regulated not only by tumor cells themselves but also by tumor cell—host cell interaction.10,17,34,36 The plasminogen activator43,46 and a variety of biologically active agents such as growth factors, cytokines, and extracellular matrix components,2,7,8,24,33,58 have been shown to regulate MMP and TIMP gene expression.
A systematic study of MMP and TIMP gene expression has not been reported in human gliomas. The present study was designed to examine the expression of five MMP (interstitial collagenase, gelatinase A, gelatinase B, stromelysin, and matrilysin) genes as well as two TIMP (TIMP-1 and TIMP-2) genes in human gliomas to evaluate the relationship between the expression levels of MMP or TIMP genes and the malignancy of gliomas. In addition, the transcriptional modulation of MMP and TIMP genes has been examined in human glioma cell line by means of treatment with phorbol-12-myristate-13-acetate (PMA), transforming growth factor-β1 (TGFβ1), epidermal growth factor (EGF), tumor necrosis factor-α (TNFα), interleukin (IL)-1β, or IL-6 (the latter five of which are detected in malignant gliomas in vivo6,12,26,47–49,57) to study their roles in glioma invasion.
Simon NNoël AFoidart JM: Evaluation of in vitro reconstituted basement membrane assay to assess the invasiveness of tumor cells. Invasion Metastasis 12:156–1671992in vitro reconstituted basement membrane assay to assess the invasiveness of tumor cells. Invasion Metastasis 12:
This work was supported by Grant-in-Aid No. 06771112 from the Ministry of Education, Science, and Culture of Japan.