Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer.
Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer.
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DOI：
10.1186/1476-4598-4-14
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发表时间：
2005-04-07
期刊：
影响因子：
37.3
通讯作者：
Friess H
中科院分区：
文献类型：
--
作者：
Li J;Kleeff J;Abiatari I;Kayed H;Giese NA;Felix K;Giese T;Büchler MW;Friess H
Hsulf-1 是一种新发现的酶，能够通过干扰肝素结合生长因子信号传导来减少肝细胞癌细胞、卵巢癌细胞和头颈鳞状细胞癌细胞的生长。由于胰腺癌过度表达多种肝素结合生长因子及其受体，因此分析了该酶在胰腺癌中的表达和功能。与正常对照相比，胰腺癌样本的 Hsulf-1 mRNA 水平显着增加（22.5 倍），并且 Hsulf-1 mRNA 定位于癌细胞本身以及瘤周成纤维细胞中。 8 个检查的胰腺癌细胞系中有 4 个表达 Hsulf-1，而其表达低于其他细胞系的检测水平。用全长 Hsulf-1 表达载体稳定转染 Hsulf-1 阴性 Panc-1 胰腺癌细胞系可导致硫酸酯酶活性增加并减少细胞表面硫酸乙酰肝素蛋白聚糖 (HSPG) 硫酸化。在该细胞系中，Hsulf-1 表达减少了贴壁依赖性和非依赖性细胞生长，并减少了 FGF-2 介导的细胞生长和侵袭。 Hsulf-1 在胰腺癌的基质成分和肿瘤细胞中高表达，并干扰肝素结合生长因子信号传导。
Hsulf-1 is a newly identified enzyme, which has the ability to decrease the growth of hepatocellular, ovarian, and head and neck squamous cell carcinoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancers over-express a number of heparin-binding growth factors and their receptors, the expression and function of this enzyme in pancreatic cancer was analyzed. Pancreatic cancer samples expressed significantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal controls, and Hsulf-1 mRNA was localized in the cancer cells themselves as well as in peritumoral fibroblasts. 4 out of 8 examined pancreatic cancer cell lines expressed Hsulf-1, whereas its expression was below the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 pancreatic cancer cell line with a full length Hsulf-1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan-sulfate proteoglycan (HSPG) sulfation. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediated cell growth and invasion in this cell line. High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling.
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