Tags

Type your tag names separated by a space and hit enter

Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.
Anticancer Res. 2002 Sep-Oct; 22(5):2539-45.AR

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.

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).

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.

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.

Authors+Show Affiliations

Department of Pharmaceutical Science, College of Pharmacy, University of Oklahoma, Health Sciences Center, 1110 N. Stonewall Ave., Oklahoma City, Oklahoma 73117, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12529961

Citation

Zang, Xiao-Ping, et al. "Specific and Non-specific KGF Inhibition of KGF-induced Breast Cancer Cell Motility." Anticancer Research, vol. 22, no. 5, 2002, pp. 2539-45.
Zang XP, Nguyen TN, Pento JT. Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility. Anticancer Res. 2002;22(5):2539-45.
Zang, X. P., Nguyen, T. N., & Pento, J. T. (2002). Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility. Anticancer Research, 22(5), 2539-45.
Zang XP, Nguyen TN, Pento JT. Specific and Non-specific KGF Inhibition of KGF-induced Breast Cancer Cell Motility. Anticancer Res. 2002 Sep-Oct;22(5):2539-45. PubMed PMID: 12529961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility. AU - Zang,Xiao-Ping, AU - Nguyen,Thao-Nguyen, AU - Pento,J Thomas, PY - 2003/1/18/pubmed PY - 2003/2/21/medline PY - 2003/1/18/entrez SP - 2539 EP - 45 JF - Anticancer research JO - Anticancer Res VL - 22 IS - 5 N2 - 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. 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). 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. 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. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/12529961/Specific_and_non_specific_KGF_inhibition_of_KGF_induced_breast_cancer_cell_motility_ L2 - https://medlineplus.gov/breastcancer.html DB - PRIME DP - Unbound Medicine ER -