Reversion of Human Glioblastoma Malignancy by U1 Small Nuclear RNA/Ribozyme Targeting of Scatter Factor/Hepatocyte Growth Factor and c-met Expression

Abounader, Roger; Ranganathan, Srikanth; Lal, Bachchu; Fielding, Kevin; Book, Adam A.; Dietz, Hal; Burger, Peter; Laterra, John

doi:10.1093/jnci/91.18.1548

Cited by 156 publications

(115 citation statements)

References 29 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…12,[34][35][36][37] Taken together with our present data, MET appears to be an important therapeutic target in the treatment of ovarian clear-cell adenocarcinomas with MET alterations, justifying the exploration of anti-MET treatment strategies. Moreover, as HGF is the only known ligand for the MET receptor, neutralization of HGF using ribozymes 38 or antagonistic fragments such as NK4, 39 and neutralizing antibodies 40 may also be the potentially attractive compounds for inhibiting HGF/MET signaling.…”

Section: Discussionmentioning

confidence: 99%

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas

et al. 2012

View full text Add to dashboard Cite

Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplificationpositive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (Z3 MET copies in Z10% and Z4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (Z4 MET copies in Z40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas

et al. 2012

View full text Add to dashboard Cite

show abstract

“…14,28 Ribozyme targeting scatter factor /hepatocyte growth factor and c-met expression has successfully reduced cell clonogenicity and inhibited tumor growth of human glioblastoma malignancy. 26 Adenovirus -mediated anti ± H -ras ribozyme has caused complete regression of the tumor in an experimental gene therapy of human bladder cancer. 29 Ribozymemediated suppression of aberrant epidermal growth factor receptor gene has been reported to inhibit the growth of tumors formed by cells expressing the aberrant gene.…”

Section: Discussionmentioning

confidence: 99%

Suppression of oncogenic viral interferon regulatory factor (vIRF) of Kaposi's sarcoma–associated herpesvirus by ribozyme-mediated cleavage

et al. 2001

View full text Add to dashboard Cite

Kaposi's sarcoma ± associated herpesvirus / human herpesvirus 8 ( KSHV / HHV8 ) has been etiologically associated with several malignancies including Kaposi's sarcoma and primary effusion lymphoma. Oncogenic viral interferon regulatory factor ( vIRF ) encoded by KSHV ORF -K9 is a homologue of cellular interferon regulatory factor ( IRF ) , and has been demonstrated to inhibit type I / II interferon signal transduction and transform NIH3T3 cells through the interactions with IRF -1, IRF -3, and CBP / p300 proteins. To counteract vIRF's pathogenic role, we have developed five ribozymes targeting ORF -K9 mRNA to suppress vIRF expression. The vIRF RNA substrates were cleaved up to 80% in a substrate -specific manner in transcript cleavage assays in vitro. In a transient transfection assay, two of the ribozymes efficiently suppressed the expression of vIRF protein measured by dual -color immunofluorescence assay that simultaneously detects the expression of both vIRF protein and ribozyme. Flow cytometry analysis showed that these ribozymes reduced vIRF expression up to 76%. A mutant ribozyme had no cleavage activity in vitro, but exhibited antisense effect in vivo. These results suggest that the ribozymes may provide a new approach for functional knockout of vIRF gene, and are potential candidates of antiviral therapy for KSHV -related malignancies. Cancer Gene Therapy ( 2001 ) 8, 285 ± 293

show abstract

“…59 Knock-down of the expression of HGF or Met by means of a ribozyme or siRNA resulted the in vitro inhibition of migration and invasion of cancer cells and the in vivo inhibition of tumor growth in distinct types of cancers, including breast cancer, glioblastoma, gastric cancer, prostate cancer, and colon cancer. [61][62][63][64][65] The knock-down of Met receptor expression by recombinant adenovirus-mediated expression of siRNA against Met resulted in the inhibition of cell growth, scattering and invasion, and an increase in apoptotic cell death in different types of tumor cells, including prostate cancer, sarcoma, glioblastoma, and gastric cancer. 61 Likewise, intratumoral infection by the adenovirus for met siRNA suppressed the growth of prostate cancer in mice.…”

Section: Therapeutic Approaches Targeting Hgf-met Systemmentioning

confidence: 99%

Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions

Matsumoto

Nakamura

2006

Intl Journal of Cancer

200

View full text Add to dashboard Cite

Crosstalk between carcinoma cells and host stromal cells such as fibroblasts has a great deal of influence on the invasive and metastatic behavior of cancer cells. The oncogenic action of fibroblasts has been demonstrated through genetic alterations that occur specifically in fibroblasts. Hepatocyte growth factor (HGF), a ligand for the Met receptor tyrosine kinase, plays a definitive role, particularly in the progression to invasive and metastatic cancers, predominantly as a stroma-derived paracrine mediator. Many types of cancer cells secrete molecules that enhance HGF production in fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. Fibroblast-specific genetic alterations leading to an overexpression of HGF are associated with the development of epithelial neoplasia and invasive carcinoma. Strategies for targeting the HGF-Met axis are being pursued, in attempts to block the malignant behavior of cancers. In normal tissues, the HGF-Met axis plays diverse roles in organogenesis and in wound healing. The simile that ''cancer is a never-healing wound'' appears to be pertinent here. ' 2006 Wiley-Liss, Inc.

show abstract

Reversion of Human Glioblastoma Malignancy by U1 Small Nuclear RNA/Ribozyme Targeting of Scatter Factor/Hepatocyte Growth Factor and c-met Expression

Cited by 156 publications

References 29 publications

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas

Suppression of oncogenic viral interferon regulatory factor (vIRF) of Kaposi's sarcoma–associated herpesvirus by ribozyme-mediated cleavage

Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions

Contact Info

Product

Resources

About