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A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth
- Source :
- Cancer Biology & Therapy. 8:2362-2370
- Publication Year :
- 2009
- Publisher :
- Informa UK Limited, 2009.
-
Abstract
- Matrix metalloproteinases (MMPs), and especially membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14), play a role in cancer progression and can have a prognostic value. Various synthetic broad-spectrum MMP inhibitors have been developed but have had little success in cancer patient treatment owing to side effects. Until recently, selective targeting of specific MMPs has not been possible due to lack of specific inhibitors. Here we have developed a selective MT1-MMP peptide-inhibitor GACFSIAHECGA, which did not affect the activities of many other MMPs including MMP-1, -2, -3, -7, -8, -9, -10, -11, -12, -13, -15, -17 or -20. In a fluorescent peptide cleavage assay it displayed an IC(50) value of 150 microM. The peptide effectively inhibited the migration and invasion of cancer cell lines in vitro. Furthermore, in vivo the peptide reduced the growth of tongue carcinoma xenografts and prolonged the survival of mice. Overall these results suggest that selective MT1-MMP inhibitors may have utility as anticancer agents.
- Subjects :
- Cancer Research
Time Factors
Cell Survival
Matrix metalloproteinase inhibitor
Motility
Antineoplastic Agents
Matrix Metalloproteinase Inhibitors
Biology
Matrix metalloproteinase
Inhibitory Concentration 50
Mice
Cell Movement
In vivo
Neoplasms
Matrix Metalloproteinase 14
medicine
Animals
Enzyme Inhibitors
Cell Proliferation
Pharmacology
Dose-Response Relationship, Drug
Cell growth
Carcinoma
Cancer
medicine.disease
Molecular biology
In vitro
Tongue Neoplasms
Oncology
Cancer cell
Cancer research
Molecular Medicine
Female
Peptides
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 15558576 and 15384047
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancer Biology & Therapy
- Accession number :
- edsair.doi.dedup.....6f867f71ae603404b16aa6334b0a3439