Untitled

Itoh, Takeshi; Tanioka, Masatoshi; Matsuda, Hitomi; Nishimoto, Hirofumi; Yoshioka, Takayuki; Suzuki, Ryuji; Uehira, Masahiro

doi:10.1023/a:1006603723759

Cited by 282 publications

(57 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a mouse model, downregulation of MMP-9 by antisense oligonucleotides reduced tumor metastasis (Kondraganti et al, 2000). In experimental metastasis assays, the number of colonies formed in the lungs of mice is reduced in the MMP-9-null mice as compared with wild-type mice (Itoh et al, 1999). Accordingly, marked inhibition of MMP-9 by ATO clearly contributes to its antimetastatic effect.…”

Section: Discussionmentioning

confidence: 95%

Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor κB

et al. 2004

View full text Add to dashboard Cite

Arsenic trioxide (ATO) has been implicated as a promising anticancer agent by inhibiting cell growth and inducing apoptosis in certain types of cancer cells. This study explored the antimetastasis property of arsenic, drew potential link between arsenic use and radiotherapy, and uncovered the specific mechanisms underlying these remarkable responses. Using gelatin invasion assay and intravasation assay, we report the novel finding that low-dose ATO (1 lM) reduced the intrinsic migration ability of HeLa cells and significantly inhibited radiation-promoted tumor invasive potential of CaSki cells without inducing apoptotic cell death. Using the murine Lewis lung carcinoma model, the control animals and ATO treatment animals (1 mg/kg i.p., twice weekly) displayed similar in vivo growth kinetics, whereas the radiation (30 Gy in one fraction) and concurrent treatment groups showed considerable growth inhibition. Importantly, although concurrent treatment did not enhance the effectiveness of radiation therapy to the primary tumor, further examination of the lungs revealed that all animals succumbed to radiation-accelerated lung metastases could be effectively treated by combination of ATO and radiation. Radiationinduced matrix metalloproteinase-9 (MMP-9) expression was significantly inhibited by ATO using sequential analysis of the expression of MMPs in xenografts. Supporting this observation, ATO directly downregulates radiation-induced MMP-9 mRNA expression by inhibiting nuclear factor jB activity in human cervical cancer cells. In sum, concurrent arsenicradiation therapy not only achieves local tumor control but also inhibits distant metastasis. Experimental results of this study highlight a novel strategy in cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 95%

Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor κB

et al. 2004

View full text Add to dashboard Cite

show abstract

“…MMP-9 inhibition in transformed keratinocytes and squamous-cell carcinoma cells was accompanied by reduced invasion through collagen and reconstituted basement membranes (Simon et al, 1998). In addition, there was a reduction in the number of lung colonies formed in an experimental metastasis system in MMP-9 null mice (Itoh et al, 1999) as well as through MMP-9 downregulation (Hua and Muschel, 1996). Our present study shows that the CMV promoter-driven expression of siRNA against cathepsin B and MMP-9 (pCM) can successfully silence cathepsin B and MMP-9 expression in the SNB19 GBM cell line, as analysed by Western blotting and gelatin zymography.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis

et al. 2004

View full text Add to dashboard Cite

Extracellular proteases have been shown to cooperatively influence matrix degradation and tumor cell invasion through proteolytic cascades, with individual proteases having distinct roles in tumor growth, invasion, migration and angiogenesis. Matrix metalloproteases (MMP)-9 and cathepsin B have been shown to participate in the processes of tumor growth, vascularization and invasion of gliomas. In the present study, we used a cytomegalovirus promoter-driven DNA template approach to induce hairpin RNA (hpRNA)-triggered RNA interference (RNAi) to block MMP-9 and cathepsin B gene expression with a single construct. Transfection of a plasmid vectorexpressing double-stranded RNA (dsRNA) for MMP-9 and cathepsin B significantly inhibited MMP-9 and cathepsin B expression and reduced the invasive behavior of SNB19, glioblastoma cell line in Matrigel and spheroid invasion models. Downregulation of MMP-9 and cathepsin B using RNAi in SNB19 cells reduced cell-cell interaction of human microvascular endothelial cells, resulting in the disruption of capillary network formation in both in vitro and in vivo models. Direct intratumoral injections of plasmid DNA expressing hpRNA for MMP-9 and cathepsin B significantly inhibited established glioma tumor growth and invasion in intracranial tumors in vivo. Further intraperitoneal (ip) injections of plasmid DNA expressing hpRNA for MMP-9 and cathepsin B completely regressed pre-established tumors for a long time (4 months) without any indication of these tumor cells. For the first time, these observations demonstrate that the simultaneous RNAi-mediated targeting of MMP-9 and cathepsin B has potential application for the treatment of human gliomas.

show abstract

“…Transforming growth factor-b is a potent growth inhibitor of normal epithelial cells, but also fosters tumor formation during later stages of tumorigenesis (Wakefield and Roberts, 2002). Transforming growth factor-b enhances the expression of MMP9, which plays significant roles during the dissemination and growth of cancer cells (Itoh et al, 1999;Coussens et al, 2000;Hiratsuka et al, 2002).…”

Section: Discussionmentioning

confidence: 99%