Abstract
Histidine-proline-rich glycoprotein (HPRG) is a plasma protein of vertebrates, which has potent antiangiogenic and tumor vessel normalization properties. Attenuated Salmonella Typhimurium strain VNP20009 preferentially accumulates and replicates in hypoxic tumor regions. In this study, we engineered VNP20009 to express HPRG under the control of a hypoxia-induced NirB promoter and evaluated the efficacy of the VNP20009-mediated targeted expressionof HPRG (VNP-pNHPRG) on tumor growth in primary and metastatic tumor models. When VNP-pNHPRG was administered to melanoma tumor mice by intraperitoneal injection, the NirB promoter controlled HPRG expression in tumor, which inhibited tumor vessel density and areas as well as regulated vascular normalization. VNP-pNHPRG significantly delayed tumor growth and enhanced survival time in primary B16F10 mice model and markedly suppressed lung metastatic tumor growth and prolonged survival time in B16F10 metastatic tumor models. Furthermore, VNP-pNHPRG down-regulated the HIF-1α-VEGF/Ang-2 signal pathway by altering the hypoxic tumor microenvironment. These results showed that VNP20009-mediated targeted expression of HPRG provides a novel cancer gene therapeutic approach for the treatment of primary and metastatic cancer.
Keywords: VNP20009, histidine-proline-rich glycoprotein, anti-angiogenesis, vessel normalization, tumor growth, tumor metastasis.
Current Gene Therapy
Title:Tumor-Specific Delivery of Histidine-Rich Glycoprotein Suppresses Tumor Growth and Metastasis by Anti-angiogenesis and Vessel Normalization
Volume: 14 Issue: 2
Author(s): Xiawei Cheng, Xiaoxin Zhang, Wei Cheng, Jianxiang Chen, Cailie Ma, Bingya Yang and Zi-Chun Hua
Affiliation:
Keywords: VNP20009, histidine-proline-rich glycoprotein, anti-angiogenesis, vessel normalization, tumor growth, tumor metastasis.
Abstract: Histidine-proline-rich glycoprotein (HPRG) is a plasma protein of vertebrates, which has potent antiangiogenic and tumor vessel normalization properties. Attenuated Salmonella Typhimurium strain VNP20009 preferentially accumulates and replicates in hypoxic tumor regions. In this study, we engineered VNP20009 to express HPRG under the control of a hypoxia-induced NirB promoter and evaluated the efficacy of the VNP20009-mediated targeted expressionof HPRG (VNP-pNHPRG) on tumor growth in primary and metastatic tumor models. When VNP-pNHPRG was administered to melanoma tumor mice by intraperitoneal injection, the NirB promoter controlled HPRG expression in tumor, which inhibited tumor vessel density and areas as well as regulated vascular normalization. VNP-pNHPRG significantly delayed tumor growth and enhanced survival time in primary B16F10 mice model and markedly suppressed lung metastatic tumor growth and prolonged survival time in B16F10 metastatic tumor models. Furthermore, VNP-pNHPRG down-regulated the HIF-1α-VEGF/Ang-2 signal pathway by altering the hypoxic tumor microenvironment. These results showed that VNP20009-mediated targeted expression of HPRG provides a novel cancer gene therapeutic approach for the treatment of primary and metastatic cancer.
Export Options
About this article
Cite this article as:
Cheng Xiawei, Zhang Xiaoxin, Cheng Wei, Chen Jianxiang, Ma Cailie, Yang Bingya and Hua Zi-Chun, Tumor-Specific Delivery of Histidine-Rich Glycoprotein Suppresses Tumor Growth and Metastasis by Anti-angiogenesis and Vessel Normalization, Current Gene Therapy 2014; 14 (2) . https://dx.doi.org/10.2174/1566523214666140305223912
DOI https://dx.doi.org/10.2174/1566523214666140305223912 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Engineered Probiotic and Prebiotic Nutraceutical Supplementations in Combating Non-communicable Disorders: A Review
Current Pharmaceutical Biotechnology Immunotherapy in Bladder Cancer
Current Molecular Pharmacology Applications of HPLC-MALDI-TOF MS/MS Phosphoproteomic Analysis in Oncological Clinical Diagnostics
Current Proteomics Editorial [Hot Topic: Anti-Cancer Drugs Executive Editor: Elke Bergmann-Leitner]
Current Pharmaceutical Design Immune Response to Herpes Simplex Virus and γ134.5 Deleted HSV Vectors
Current Gene Therapy Electrotransfer into Skeletal Muscle for Protein Expression
Current Gene Therapy Schiff Bases and Complexes: A Review on Anti-Cancer Activity
Anti-Cancer Agents in Medicinal Chemistry Anaesthesia in Cancer Surgery: Can it Affect Cancer Survival?
Current Clinical Pharmacology Hydroxychloroquine (HCQ) and its Synthetic Precursors: A Review
Mini-Reviews in Organic Chemistry Targeting Regulatory T Cells for Anticancer Therapy
Mini-Reviews in Medicinal Chemistry Vaccine Therapy of Melanoma: An Update
Current Cancer Therapy Reviews Patent Selections
Recent Patents on Food, Nutrition & Agriculture Targeting DNA Repair Proteins: A Promising Avenue for Cancer Gene Therapy
Current Gene Therapy The Role of Thrombomodulin in Atherosclerosis: From Bench to Bedside
Cardiovascular & Hematological Agents in Medicinal Chemistry Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics Biomarkers and Novel Therapeutic Targets in Gastrointestinal Stromal Tumors (GISTs)
Recent Patents on Anti-Cancer Drug Discovery Apoptotic Effects of Bilirubin on Skin Cancer Cell Lines SK-MEL-3 (Melanoma) and A431 (Non-Melanoma)
Anti-Cancer Agents in Medicinal Chemistry Recent Developments in Boron Neutron Capture Therapy (BNCT) Driven by Nanotechnology
Current Chemical Biology In Vitro Evaluation of Antimicrobial and Antiproliferative Activities for Compounds Isolated from the Ficus Bubu Warb. (Moraceae) Fruits: Chemotaxonomic Significance
Drug Delivery Letters Inhibition of V-ATPase and Carbonic Anhydrases as Interference Strategy with Tumor Acidification Processes
Current Pharmaceutical Design