Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy
Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy
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DOI：
10.1016/j.oraloncology.2006.10.010
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发表时间：
2007-10-01
期刊：
影响因子：
4.8
通讯作者：
Mizuno, Akio
中科院分区：
文献类型：
--
作者：
Yanamoto, Souichi;Kawasaki, Goro;Mizuno, Akio
上皮细胞。粘附分子（EpCAM）是一种参与细胞间粘附的跨膜糖蛋白。尤其是，EpCAM 似乎在大多数人类上皮细胞中过度表达。癌症，包括结直肠癌、乳腺癌、头颈癌和肝癌。因此，我们假设 EpCAM 将是癌症基因治疗的良好分子靶点。采用抗EpCAM免疫组化方法检测48例原发性舌癌和10例正常口腔黏膜组织中EpCAM蛋白的表达，并探讨其与临床病理因素的相关性。在四种人舌癌细胞（SAS、HSC-2、OSC19 和 OSC20）中，我们通过逆转录聚合酶链反应（RT-PCR）研究了 EpCAM 的表达。使用基质胶侵袭测定评估癌细胞的侵袭潜力。此外，使用 RNA 干扰 (RNAi) 分析了 EpCAM 抑制的效果。 EpCAM 在 48 例舌癌中的 30 例 (62.5%) 中检测到过表达，并且在舌原发性鳞状细胞癌 (SCC) 中的表达显着高于正常口腔粘膜。 EpCAM的表达与肿瘤大小、区域淋巴结转移、组织学分化和侵袭模式显着相关。 EpCAM 表达较高的癌细胞具有更大的侵袭潜力。此外，RNAi介导的EpCAM减少降低了侵袭潜力和增殖活性。这些结果表明 EpCAM 的过度表达与舌癌更具侵袭性的表型相关。此外，我们认为 EpCAM 可能是一个分子靶点，而针对 EpCAM 的 RNAi 可能有助于舌癌基因治疗。 (c) 2006 Elsevier Ltd. 保留 Alt 权利。
Epithelial. adhesion molecule (EpCAM) is a transmembrane glycoprotein involved in intercellular adhesion. In particular, EpCAM appears to be overexpressed by the majority of human epithelial. carcinomas, including colorectal, breast, head and neck, and hepatic carcinomas. We therefore hypothesized that EpCAM would be a good molecular target for cancer gene therapy. EpCAM protein expression in 48 primary tongue cancers and 10 normal oral mucosa was evaluated using anti-EpCAM immunohistochemistry, and correlation was examined with the clinico patho logic factors. In four human tongue cancer cell tines (SAS, HSC-2, OSC19 and OSC20), we investigated EpCAM expression by reverse transcription-polymerase chain reaction (RT-PCR). The invasive potential of cancer cells was evaluated using Matrigel invasion assay. Moreover, the effect of EpCAM inhibition was analyzed using RNA interference (RNAi). EpCAM overexpression was detected in 30 of 48 tongue cancers (62.5%), and was significantly higher in primary squamous cell carcinoma (SCC) of the tongue than in normal, oral mucosa. The expression of EpCAM was significantly associated with tumor size, regional lymph node metastasis, histological differentiation and invasion pattern. Cancer cell tines with higher EpCAM expression had more invasive potential. Moreover, RNAi-mediated EpCAM reduction decreased the invasion potential and proliferation activity. These results indicated that the overexpression of EpCAM was correlated with a more aggressive phenotype of tongue cancer. Moreover, we suggested that EpCAM could be a molecular target, and that RNAi targeting EpCAM could be useful for tongue cancer gene therapy. (c) 2006 Elsevier Ltd. Alt rights reserved.