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Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.
- Source :
-
Anticancer research [Anticancer Res] 2002 Sep-Oct; Vol. 22 (5), pp. 2539-45. - Publication Year :
- 2002
-
Abstract
- Background: Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is a mesenchymally derived mediator of epithelial cell proliferation and migration. In a previous study, we reported that KGF enhanced the motility of human breast cancer cells. The objective of the present study was to examine the influence of specific and non-specific KGF inhibitors on KGF-induced motility and proliferation in ER-positive MCF-7 cells.<br />Materials and Methods: In the present study three KGF inhibitors were employed [Heparin, Innohep, a low molecular weight heparin (LMWH) and KGFR2 beta (IIIb)/Fc, a chimeric KGFR fragment]. Heparin and LMWH bind to low affinity sites on KGF and produce non-specific inhibition, while KGFR2 beta (IIIb)/Fc, a soluble chimera of an extracellular KGFR fragment, is a more specific KGF inhibitor. Cellular motility was measured using two methods: culture wounding over a period of 48 hours; and secondly, time-lapse videomicroscopy (TLVM).<br />Results: In these experiments KGF was found to produce a dose-dependent enhancement of MCF-7 cell motility over a dosage range of 5 to 500 ng/ml. In the TLVM experiments, Heparin (30 ng/ml), LMWH (30 ng/ml) and KGFR2 beta (IIIb)/Fc (50 micrograms/ml) completely inhibited KGF-induced motility of MCF-7 cells during the initial 2-hour observation period. In the culture wounding assay, LMWH produced a greater reduction in KGF-induced motility than heparin at 48 hours post-treatment.<br />Conclusion: The results of this study indicate that KGF-mediated enhancement of breast cancer cells motility and proliferation is inhibited by both specific and non-specific KGF inhibitors. LMWH appears to produce an inhibition of KGF with a much longer duration of action than Heparin. Our results suggest that KGF inhibition may be a potential new therapeutic approach for the treatment of metastatic breast cancer.
- Subjects :
- Cell Division drug effects
Cell Division physiology
Cell Movement physiology
Dose-Response Relationship, Drug
Fibroblast Growth Factor 7
Fibroblast Growth Factors pharmacology
Heparin pharmacology
Heparin, Low-Molecular-Weight pharmacology
Immunoglobulin Fc Fragments pharmacology
Microscopy, Video
Peptide Fragments pharmacology
Receptor, Fibroblast Growth Factor, Type 2
Receptors, Fibroblast Growth Factor chemistry
Recombinant Fusion Proteins pharmacology
Recombinant Proteins antagonists & inhibitors
Recombinant Proteins pharmacology
Substrate Specificity
Tumor Cells, Cultured
Breast Neoplasms pathology
Cell Movement drug effects
Fibroblast Growth Factors antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 22
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 12529961