Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth

Horiguchi, Akio; Zheng, Rong; Goodman, Oscar B.; Shen, Ruoqian; Guan, Hao; Hersh, Louis B.; Nanus, David M.

doi:10.1038/sj.cgt.7701047

Cited by 12 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37,38 Most of them use recombinant adenoviruses or lentiviruses, 39,40 but because of the possibility of recombination with wildtype adenovirus and the antiviral immune response, these approaches have been limited to research use. 41 More recently, electroporation has been applied in vivo and shown to be potentially safe for clinical use.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Zhang

Zhao

et al. 2009

Cancer Gene Ther

View full text Add to dashboard Cite

The destruction of extracellular matrix by matrix metalloproteinases is a key event in cancer progression. The tissue inhibitors of metalloproteinases can restrain tumor growth by inhibiting these enzymes. We sought to determine whether overexpression of tissue inhibitor of metalloproteinase-3 (TIMP-3) could suppress the malignant phenotype of human prostate cancer cell line PC-3M. Stable overexpression of TIMP-3 inhibited cell proliferation significantly by MTT assay. Both early and late apoptosis were observed in TIMP-3 overexpressing cells, and flow cytometry analysis showed S-phase blocking of the cell cycle. Monolayer invasion assay and transwell invasion assay showed significantly decreased invasive potential in TIMP-3 overexpressing cells compared with control cells. Cell adhesion and motility were also lower after TIMP-3 was overexpressed. In vivo, cells stably overexpressing TIMP-3 completely lost the ability to form tumors after injection into nude mice. Transfection of TIMP-3 into established tumors by electroporation also had a significant antitumor effect. TIMP-3-treated tumor tissues had significant apoptosis by TUNEL assay. These results showed that overexpression of TIMP-3 inhibits invasion and proliferation of prostate cancer cells in vitro and inhibits tumor growth in vivo. The experiments suggest a potential use for TIMP-3 in the gene therapy of prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Zhang

Zhao

et al. 2009

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…Second, gene-therapy approaches targeting protease genes can intrinsically improve proper protease activity. This approach has been show to work in lentiviral-mediated neprilysin gene transfer to block prostate cancer growth 6. Third, an indirect approach is to hamper protease inhibitors to reduce protective (anti-tumor) proteases.…”

Section: Introductionmentioning

confidence: 99%

Protease-Activated Drug Development

Choi¹,

Swierczewska²,

Lee³

et al. 2012

Theranostics

205

189

View full text Add to dashboard Cite

In this extensive review, we elucidate the importance of proteases and their role in drug development in various diseases with an emphasis on cancer. First, key proteases are introduced along with their function in disease progression. Next, we link these proteases as targets for the development of prodrugs and provide clinical examples of protease-activatable prodrugs. Finally, we provide significant design considerations needed for the development of the next generation protease-targeted and protease-activatable prodrugs.

show abstract

“…In prostate cancer cell lines, there is a reciprocal relation between expression levels of the ET‐1 synthetic enzyme, endothelin‐converting enzyme‐1 (ECE‐1) and the ET‐1 degrading enzyme, NEP 2. Hence, downregulation of ECE‐110 or upregulation of NEP11 are proposed as viable therapeutic strategies in advanced prostate cancer.…”

mentioning

confidence: 99%

The impact of amyloid precursor protein signalling and histone deacetylase inhibition on neprilysin expression in human prostate cells

Beckett

Belyaev

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

The zinc metallopeptidase, neprilysin (NEP), is an endothelin-1 degrading enzyme whose expression is extensively downregulated in prostate cancer. The expression of NEP in neuronal cells is regulated by intramembrane proteolysis of the amyloid precursor protein (APP) through its intracellular domain (AICD) facilitating histone acetylation of the NEP promoter and gene transcription. The present study has examined whether similar mechanisms operate in prostate cell lines. The expression of APP and its processing enzymes (b-and c-secretases) was examined in a number of prostate cell lines, and the effect of c-secretase inhibition was explored on NEP expression and activity. The potential interaction of AICD with the NEP promoter was examined by chromatin immunoprecipitation. Our results indicated that all key components involved in APP processing were expressed in prostate cancer cell lines but suppression of AICD production using a c-secretase inhibitor did not decrease NEP expression and activity, and no direct AICD-NEP promoter interaction could be detected. However, histone deacetylase inhibitors (valproate and trichostatin A) caused a 2-to 3-fold increase in NEP expression in PC-3 cells, and combinatorial treatment with the DNA demethylating agent, AzaC, further increased NEP expression levels. Although AICD is detectable in prostate cell lines, it does not appear to regulate NEP by AICD-mediated signalling. Apart from promoter demethylation, the data suggest that histone acetylation may facilitate partial re-activation of NEP expression in advanced prostate cancer cells. Upregulation of this tumour-suppressing protein may provide a novel therapeutic strategy in prostate cancer.Prostate cancer (PC) is the most frequently diagnosed cancer in western males. Advanced PC in the androgen-independent, chemo-refractory state is extremely life-threatening and currently incurable. In the progression of PC to the more malignant, androgen-independent phenotype, loss of a membrane-bound zinc metallopeptidase, neprilysin (NEP), is commonly found.1,2 NEP is an integral membrane glycoprotein and ectoenzyme which serves to inactivate circulating regulatory peptides.3 NEP has a wide tissue expression including intestinal and kidney epithelium, brain, skeletal muscle, lung and prostate. [4][5][6][7][8] NEP is able to inhibit cancer cell proliferation, migration and promote cell apoptosis during chemotherapy either via degradation of mitogenic neuropeptides such as endothelin-1 (ET-1), or by its direct protein-protein interactions with tumour suppressor PTEN, phosphatidylinositol 3-kinase (PI3K) and ezrin/radixin/moesin (ERM) proteins. 9 In prostate cancer cell lines, there is a reciprocal relation between expression levels of the ET-1 synthetic enzyme, endothelin-converting enzyme-1 (ECE-1) and the ET-1 degrading enzyme, NEP.2 Hence, downregulation of ECE-1 10 or upregulation of NEP 11 are proposed as viable therapeutic strategies in advanced prostate cancer.In the prostate, NEP expression is positively regulated by androgens, ...

show abstract

Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth

Cited by 12 publications

References 26 publications

Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Inhibition of tumor growth and induction of apoptosis in prostate cancer cell lines by overexpression of tissue inhibitor of matrix metalloproteinase-3

Protease-Activated Drug Development

The impact of amyloid precursor protein signalling and histone deacetylase inhibition on neprilysin expression in human prostate cells

Contact Info

Product

Resources

About