Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.
Specific and non-specific KGF inhibition of KGF-induced breast cancer cell motility.
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发表时间：
2002-09
影响因子：
2
通讯作者：
X. Zang;Thao Nguyen;J. Pento
中科院分区：
文献类型：
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作者：
X. Zang;Thao Nguyen;J. Pento
角质形成细胞生长因子（KGF）是成纤维细胞生长因子家族的成员，是上皮细胞增殖和迁移的间充质来源的介质。在以前的研究中，我们报道了KGF增强了人乳腺癌细胞的运动性。本研究的目的是研究特异性和非特异性KGF抑制剂对KGF诱导的ER阳性MCF-7细胞运动和增殖的影响。材料和方法在本研究中，使用了三种KGF抑制剂[肝素、Innohep，一种低分子量肝素（LMWH）和KGFR 2 β（IIIb）/Fc，一种嵌合KGFR片段]。肝素和LMWH与KGF上的低亲和力位点结合并产生非特异性抑制，而KGFR 2 β（IIIb）/Fc（细胞外KGFR片段的可溶性嵌合体）是一种更特异的KGF抑制剂。使用两种方法测量细胞运动性：48小时内培养创伤;其次，延时视频显微镜（TLVM）。结果在这些实验中，发现KGF在5至500 ng/ml的剂量范围内产生剂量依赖性的MCF-7细胞运动性增强。在TLVM实验中，肝素（30 ng/ml）、LMWH（30 ng/ml）和KGFR 2 β（IIIb）/Fc（50 μ g/ml）在最初2小时的观察期内完全抑制了MCF-7细胞的KGF诱导运动性。在培养物损伤试验中，LMWH在治疗后48小时比肝素产生更大的KGF诱导的运动性降低。结论KGF对乳腺癌细胞运动和增殖的促进作用受到特异性和非特异性KGF抑制剂的抑制。LMWH对KGF的抑制作用似乎比肝素持续时间长得多。我们的研究结果表明，KGF抑制可能是一个潜在的新的治疗方法，用于治疗转移性乳腺癌。
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.