ArticleGene therapy2012
Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors.
Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 66 citations in OpenAlex.
- Nanotechnology-enabled gene delivery for cancer and other genetic diseases.Expert opinion on drug delivery · 2023Review
- Claudin and pancreatic cancer.Frontiers in oncology · 2023Review
- Differential Expression of Claudin 1 and 4 in Basal Cell Carcinoma of the Skin.Dermatology research and practice · 2023Article
- Research progress on the relationship between intestinal microecology and intestinal bowel disease.Animal models and experimental medicine · 2022Review
- Application of C-Terminal Clostridium Perfringens Enterotoxin in Treatment of Brain Metastasis from Breast Cancer.Cancers · 2022Review
- From Immunotoxins to Suicide Toxin Delivery Approaches: Is There a Clinical Opportunity?Toxins · 2022Review
- Identifying luminal and basal mammary cell specific genes and their expression patterns during pregnancy.PloS one · 2022Article
- A Brief Introduction to Current Cancer Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Effective Oncoleaking Treatment of Pancreatic Cancer by Claudin-Targeted Suicide Gene Therapy withCancers · 2021Article
- CITED4 enhances the metastatic potential of lung adenocarcinoma.Thoracic cancer · 2021Article
- Prostate Microbiota and Prostate Cancer: A New Trend in Treatment.Frontiers in oncology · 2021Review
- Microbiome in human cancers.Access microbiology · 2021Review
- Targeting claudin-overexpressing thyroid and lung cancer by modified Clostridium perfringens enterotoxin.Molecular oncology · 2020Article
- Impact of chemotherapy on the expression of claudins and cadherins in invasive breast cancer.Experimental and therapeutic medicine · 2019Article
- Use of ModifiedInternational journal of molecular sciences · 2019Article
- Targeting claudin-3 suppresses stem cell-like phenotype in nonsquamous non-small-cell lung carcinoma.Lung cancer management · 2019Article
- Claudin-3 Inhibits Lung Squamous Cell Carcinoma Cell Epithelial-mesenchymal Transition and Invasion via Suppression of the Wnt/β-catenin Signaling Pathway.International journal of medical sciences · 2018Article
- Multiple protocadherins are expressed in brain microvascular endothelial cells and might play a role in tight junction protein regulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker.Molecular & cellular proteomics : MCP · 2017Article
- Claudin-3 expression increases the malignant potential of lung adenocarcinoma cells: role of epidermal growth factor receptor activation.Oncotarget · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial toxins are known to be effective for cancer therapy. Clostridium perfringens enterotoxin (CPE) is produced by the bacterial Clostridium type A strain. The transmembrane proteins claudin-3 and -4, often overexpressed in numerous human epithelial tumors (for example, colon, breast, pancreas, prostate and ovarian), are the targeted receptors for CPE. CPE binding to them triggers formation of membrane pore complexes leading to rapid cell death. In this study, we aimed at selective tumor cell killing by CPE gene transfer. We generated expression vectors bearing the bacterial wild-type CPE cDNA (wtCPE) or translation-optimized CPE (optCPE) cDNA for in vitro and in vivo gene therapy of claudin-3- and -4-overexpressing tumors. The CPE expression analysis at messenger RNA and protein level revealed more efficient expression of optCPE compared with wtCPE. Expression of optCPE showed rapid cytotoxic activity, hightened by CPE release as bystander effect. Cytotoxicity of up to 100% was observed 72 h after gene transfer and is restricted to claudin-3-and -4-expressing tumor lines. MCF-7 and HCT116 cells with high claudin-4 expression showed dramatic sensitivity toward CPE toxicity. The claudin-negative melanoma line SKMel-5, however, was insensitive toward CPE gene transfer. The non-viral intratumoral in vivo gene transfer of optCPE led to reduced tumor growth in MCF-7 and HCT116 tumor-bearing mice compared with the vector-transfected control groups. This novel approach demonstrates that CPE gene transfer can be employed for a targeted suicide gene therapy of claudin-3- and -4-overexpressing tumors, leading to the rapid and efficient tumor cell killing in vitro and in vivo.
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