High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer:: A predictive molecular marker of metachronous liver and lung metastases
High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer:: A predictive molecular marker of metachronous liver and lung metastases
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DOI：
10.1158/1078-0432.ccr-04-0485
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发表时间：
2004-11-01
影响因子：
11.5
通讯作者：
Yokozaki, H
中科院分区：
文献类型：
--
作者：
Kato, H;Semba, S;Yokozaki, H
目的：PRL-3过表达与结直肠癌转移有关。我们研究了PRL-3的表达在结直肠癌的进展和发展中的意义。实验设计：我们转染PRL-3特异性小干扰RNA到人结肠癌DLD-1细胞中，并分析其对增殖，运动和肝定植的影响。使用原位杂交方法，我们检测了PRL-3在两个原发性卵巢癌中的表达水平。（177例）和转移性92例结直肠癌患者的临床病理资料，并阐明其与原发肿瘤根治性手术后异时性肝和/或肺转移发生率等临床病理参数的关系。DLD-1细胞中PRL-3表达的瞬时下调废除了运动性（体外）和肝定植（体内），但未观察到对这些细胞增殖的影响。在原发性结直肠癌中，PRL-3在肝转移（84.4%）或肺转移（88.9%）的病例中表达上调的频率显著高于无任何类型转移的病例（肝，35.9%;肺，42.3%）。在转移性结直肠癌病变中，经常检测到PRL-3的高表达（肝，91.3%;肺，100%）。结论：PRL-3在结直肠癌组织中的表达可能与肝转移的发生有关，尤其是在癌细胞脱离血循环向肝组织浸润的过程中。此外，PRL-3有望成为一种有前途的生物标志物，用于识别具有远处转移高风险的结直肠癌患者。
Purpose: Overexpression of PRL-3 has been implicated in colorectal cancer metastases. We investigated the significance of PRL-3 expression in the progression and development of colorectal cancer.Experimental Design: We transfected PRL-3-specific small interfering RNA into human colon cancer DLD-1 cells and analyzed its effect on proliferation, motility, and hepatic colonization. Using an in situ hybridization method, we examined the levels of PRL-3 expression in both primary (177 cases) and metastatic (92 cases) human colorectal cancers and elucidated the relationships with clinicopathological parameters including the incidence of metachronous liver and/or lung metastasis after curative surgery for primary tumor.Results: Transient down-regulation of PRL-3 expression in DLD-1 cells abrogated motility (in vitro) and hepatic colonization (in vivo), but no effect on the proliferation of these cells was observed. In human primary colorectal cancers, the frequency of up-regulated PRL-3 expression in cases with liver (84.4%) or lung (88.9%) metastasis was statistically higher than that in cases without either type of metastasis (liver, 35.9%; lung, 42.3%). In metastatic colorectal cancer lesions, high expression of PRL-3 was frequently detected (liver, 91.3%; lung, 100%). Interestingly, metachronous metastasis was observed more frequently in the cases with high PRL-3 expression (P < 0.0001).Conclusions: These results indicate that PRL-3 expression in colorectal cancers may contribute to the establishment of liver metastasis, particularly at the step in which cancer cells leave the circulation to extravasate into the liver tissue. In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases.