Heparanase expression correlates with malignant potential in human colon cancer
Heparanase expression correlates with malignant potential in human colon cancer
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DOI：
10.1007/s00432-004-0644-x
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发表时间：
2005-04-01
影响因子：
3.6
通讯作者：
Tanaka, N
中科院分区：
文献类型：
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作者：
Nobuhisa, T;Naomoto, Y;Tanaka, N
目的：肝素酶切割硫酸肝素蛋白多糖的碳水化合物链，是细胞外基质的重要组成部分。本研究旨在探讨肝素酶表达与结肠癌患者预后的关系。方法：研究对象为1992年1月至1994年12月间行结直肠癌切除术的54例患者（男35例，女19例）。检测肝素酶蛋白和mRNA的表达，并与各种临床病理参数进行相关性分析。我们还进行了体外研究以检查肿瘤侵袭和肝素酶抑制的效果，并进行了体内研究以检查肿瘤转移和预后。结果：54例结肠癌中37例（69%）在肿瘤侵袭前检测到肝素酶表达，而54例肿瘤中17例（31%）呈阴性。肝素酶在TNM分期高（P=0.0481）、Dukes分期高（P=0.0411）、血管浸润程度高（P=0.0146）、淋巴管浸润程度高（P=0.0010）的肿瘤中表达较多。肝素酶在结肠癌中的表达与生存率有显著相关性（P=0.0361）。与对照组相比，转染肝素酶的结肠癌细胞表现出明显的侵袭性（P=0.001），并且通过结节数量（P=0.017）和存活率（P=0.0062）检测，肝素酶转染的结肠癌细胞在腹膜播散模型中也显示出了恶性潜能。抑制肝素酶可显著降低癌细胞的侵袭能力（P=0.003）。结论：肝素酶是结肠癌患者预后不良的标志物，可作为结肠癌抗肿瘤治疗的合适靶点。
Purpose: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. Methods: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. Results: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003). Conclusions: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.