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Novel pegylated interferon‐β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer
- Source :
- Cancer Science
- Publication Year :
- 2017
- Publisher :
- John Wiley and Sons Inc., 2017.
-
Abstract
- Malignant ascites manifests as an end-stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon-β (IFN-β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN-β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN-β, each conjugated with a polyethylene glycol molecule (PEG-hIFN-β and PEG-mIFN-β, respectively). We provide evidence that these IFN-β molecules retain anti-viral potency comparable to unmodified IFN-β in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG-mIFN-β significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG-hIFN-β directly suppresses VEGF165 -induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG-mIFN-β enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN-β in maintaining vascular integrity, and provide proof-of-mechanism for a novel and long-acting pegylated hIFN-β for the therapeutic treatment of malignant ascites.
- Subjects :
- 0301 basic medicine
Vascular Endothelial Growth Factor A
Cancer Research
Pathology
Cell Membrane Permeability
Gene Expression
Vascular permeability
Mice, SCID
Polyethylene Glycols
0302 clinical medicine
Basic and Clinical Immunology
Pegylated interferon
Ascites
Medicine
Anti‐tumor activity
5'-Nucleotidase
Cells, Cultured
Peritoneal Neoplasms
pegylated interferon‐beta
Oligonucleotide Array Sequence Analysis
Mice, Knockout
Mice, Inbred BALB C
General Medicine
Oncology
030220 oncology & carcinogenesis
peritoneal metastasis
Area Under Curve
Original Article
medicine.symptom
vascular hyperpermeability
medicine.drug
medicine.medical_specialty
Metabolic Clearance Rate
Mice, Nude
Antiviral Agents
03 medical and health sciences
In vivo
Cell Line, Tumor
Human Umbilical Vein Endothelial Cells
Animals
Humans
Cell adhesion
business.industry
Cancer
malignant ascites
Original Articles
Interferon-beta
medicine.disease
Xenograft Model Antitumor Assays
In vitro
Mice, Inbred C57BL
030104 developmental biology
Cancer research
business
Ovarian cancer
Subjects
Details
- Language :
- English
- ISSN :
- 13497006 and 13479032
- Volume :
- 108
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....d78dfd6b9667bb497f6ecafcf367c2bf