Περίληψη:
Increases in the abundance of cathepsin B transcript and protein with
increased tumor grade and changes in subcellular localization and
activity of this enzyme. We observed progressive reductions in levels of
the protease inhibitor cystatin C, an inhibitor of cathepsin B with
corresponding increases in the malignancy of glioma cell lines, implying
an inverse correlation between cystatin C and tumor grade. To
investigate the role of cystatin C in the invasion of brain tumor cells,
we stably transfected SNB19 glioblastoma cells with either a 0.4-kb cDNA
construct of human cystatin C in the sense orientation or an empty
vector. Clones expressing sense-cystatin C cDNA had higher cystatin C
mRNA and protein levels than did control cells. Sense-transfected cells
were also markedly less invasive than control cells in a Matrigel
invasion assay and in a coculture assay of SNB19 spheroids and fetal rat
brain aggregates. Finally, the sense-transfected cells did not form
tumors in nude mice upon intracerebral injection. These results strongly
implicate cystatin C in the invasiveness of human glioblastoma cells and
suggest that sense transcripts of cystatin C may prove useful in cancer
therapy.
Συγγραφείς:
Konduri, SD
Yanamandra, N
Siddique, K
Joseph, A
Dinh, DH
and Olivero, WC
Gujrati, M
Kouraklis, G
Swaroop, A and
Kyritsis, AP
Rao, JS
