Elevated membrane-type matrix metalloproteinases in gliomas revealed by profiling proteases and inhibitors in human cancer cells.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate proteolysis of the extracellular matrix and other extracellular proteins, including growth factors and their receptors. The aberrant expression of these genes is common in most cancers. We profiled the RNA levels of every human MMP and TIMP in a variety of cell types (fibroblast, endothelial, hematopoietic, carcinoma, melanoma, and glioma) using quantitative PCR, with the aim of identifying novel expression patterns. Almost all members of the membrane-type (MT-) MMP and TIMP families were elevated in glioma lines compared to carcinomas. In clinical glioma specimens, there were positive correlations between glioma grade and RNA levels of MT-1, MT-2, and MT-6 MMP, TIMP-1 and TIMP-2, and for several growth factors and receptors. These findings suggest that advanced malignant gliomas have elevated levels of membrane-associated MMPs and TIMPs, which may potentially regulate vascularization and invasion. Concurrent elevation of signaling molecules suggests potential bidirectional relationships that enhance tumor aggressiveness.
Nuttall
Robert K
RK
School of Biological Sciences, University of East Anglia, Norwich, Norfolk, United Kingdom.
Pennington
Caroline J
CJ
Taplin
Jennifer
J
Wheal
Alison
A
Yong
Voon Wee
VW
Forsyth
Peter A
PA
Edwards
Dylan R
DR
D001932:Brain Neoplasms; D002277:Carcinoma; D017931:DNA Primers; D004727:Endothelium / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005354:Fibrosarcoma; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma; D019337:Hematologic Neoplasms; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008545:Melanoma; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases