Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that there is a correlation between tumor cell efficiency in activation of matrix metalloproteinase-2 (MMP-2) and invasion through basement membrane-like Matrigel barriers. To generate cells capable of MMP-2 activation, we stably transfected three human tumor cell lines, HT-1080 fibrosarcoma, MCF7 breast carcinoma, and U251.3 glioma with cDNA encoding the full length human membrane-type matrix metalloproteinase-1. Our results show a bimodal correlation between the extent of MMP-2 activation and Matrigel invasion by tumor cells. Cell transfectants characterized by a partial activation of MMP-2 were the most invasive while those with an extensive conversion of MMP-2 proenzyme into enzymatically active forms were the least efficient in invading Matrigel. Modulation of MMP-2 activation by exogenous TIMP-2 reverted the rate of Matrigel invasion by cell transfectants to control levels. We conclude that the regulation of activated MMP-2 in the tumor cells, microenvironment may be critical in facilitating tumor cell invasiveness.
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PMID:Tumor cell invasion through matrigel is regulated by activated matrix metalloproteinase-2. 941 49

Glioblastoma (GBM) is one of the most aggressive primary brain tumors with frequent recurrences following the standard methods of treatment-temozolomide (TMZ), ionizing radiation and surgical resection. The objective of our study was to investigate GBM resistance mediated via MMP14 (matrix metalloproteinase 14). We used multiple PDX GBM models and established glioma cell lines to characterize expression and subcellular localization of MMP14 after TMZ treatment. We performed a Kiloplex ELISA-based array to evaluate changes in cellular proteins induced by MMP14 expression and translocation. Lastly, we conducted functional and mechanistic studies to elucidate the role of DLL4 (delta-like canonical notch ligand 4) in regulation of glioma stemness, particularly in the context of its relationship to MMP14. We detected that TMZ treatment promotes nuclear translocation of MMP14 followed by extracellular release of DLL4. DLL4 in turn stimulates cleavage of Notch3, its nuclear translocation and induction of sphering capacity and stemness.
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PMID:TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway. 3144 14