Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion
Φόρτωση...
Ημερομηνία
Συγγραφείς
Kondraganti, S.
Mohanam, S.
Chintala, S. K.
Kin, Y.
Jasti, S. L.
Nirmala, C.
Lakka, S. S.
Adachi, Y.
Kyritsis, A. P.
Ali-Osman, F.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Cancer Res
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vector capable of expressing an antisense transcript complementary to a 528-bp segment at the 5' end of human MMP-9 cDNA. Stable transfectants were obtained through selection with G418. Of the clones transfected with vector, sense, and antisense constructs, Northern blotting, Western blotting, and gelatin zymography showed that MMP-9 expression was significantly reduced only in the antisense-transfected cells. A Matrigel invasion assay revealed marked reductions in invasiveness for the antisense clones relative to the parental, vector, and sense clones. Cocultures of tumor spheroids and fetal rat brain aggregates showed that the antisense-transfected stable clones showed no invasion of the rat brain aggregates; in contrast, 90% of the parental, vector, and sense clones invaded the rat brain aggregates. Intracerebral injection of antisense stable transfectants in nude mice produced no tumors or very small tumors, but intracerebral injection of parental or vector clones did produce tumors. These results suggest that MMP-9 expression is essential for the invasiveness of glioblastoma cells.
Περιγραφή
Λέξεις-κλειδιά
Animals, Blotting, Northern, Blotting, Western, Brain/metabolism, Cell Line, Cells, Cultured, Coculture Techniques, Collagen/metabolism, DNA, Complementary/metabolism, Down-Regulation, Drug Combinations, *Gene Transfer Techniques, Glioblastoma/*drug therapy/*enzymology/*genetics, Humans, Laminin/metabolism, Matrix Metalloproteinase 9/*metabolism, Mice, Mice, Nude, Microscopy, Confocal, Neoplasm Invasiveness, Neoplasm Transplantation, Oligonucleotides/pharmacology, Oligonucleotides, Antisense/*pharmacology, Plasmids/metabolism, Proteoglycans/metabolism, RNA, Messenger/metabolism, Rats, Time Factors, Transfection
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/11156378
http://cancerres.aacrjournals.org/content/60/24/6851.full.pdf
http://cancerres.aacrjournals.org/content/60/24/6851.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής