The Mechanism of Human Esophageal Cancer lnvasion and Metastasis

我们研究了细胞间粘附分子E-钙粘蛋白（ECD）在人食管癌侵袭和转移中的作用。使用培养的人食管癌细胞系（TE-2），建立了ECD阳性（+）和ECD阴性（-）细胞系。ECD（+）细胞具有较强的细胞间粘附，而ECD（-）细胞具有较强的迁移。在培养液中加入人抗ECD单克隆抗体（HECD-1）不改变ECD（-）细胞的迁移，但抑制ECD（+）细胞的粘附，促进其迁移。这些结果表明，癌细胞的迁移和侵袭可能会增强ECD的减少或损失。使用相同的实验系统，我们还评估了表皮生长因子（EGF），通过EGF受体（EGFR）的作用，对ECD-Ephi连环蛋白细胞间粘附系统的影响。1)聚集试验：ECD（+）细胞在软琼脂上培养时，聚集成球。加入EGF后， 关于我们 细胞仅形成小的单层团块。当培养ECD（-）细胞时，它们变成成纤维细胞样，加入EGF没有影响。2)ECD表达的改变：ECD（+）细胞显示出强ECD表达，仅限于细胞膜，但加入EGF后，ECD表达在细胞中变得广泛。3)侵袭：当ECD（+）细胞在含胶原的成纤维细胞上培养时，它们形成多层团块。加入EGF后，它们可以渗透到凝胶中。免疫印迹分析：ECD（+）细胞与EGF和抗ECD单克隆抗体（HECD-1）共同孵育产生免疫沉淀，并检测磷酸化酪氨酸的存在。EGF-EGFR结合后，E-catenin转化为磷酸酪氨酸，提示EGF-EGFR结合影响了cadoherin-catenin系统，导致细胞间粘附机制的某些异常。一项对人食管癌组织的化疗研究表明，在肿瘤显示ECD或Ephi-catenin表达降低的患者中，淋巴结转移频繁发生，预后不良。【概要】细胞间粘附异常，如ECD或Ephi catenin的减少以及EGF诱导的beta catenin磷酸化，可能与人食管癌的侵袭和转移有关。少

We studied the role of an intercellular adhesion molecule, E-cadherin (ECD), in invasion and metastasis of human esophageal cancer. Using a cultured human esophageal cancer cell line (TE-2), ECD-positive (+) and ECD negative (-) cell lines were established. The ECD (+) cells demonstrated stronger intercellular adhesion, while ECD (-) cells showed more prominent migration. Addition of a human anti-ECD mAb (HECD-1) to cultures didnot alter the migration of ECD (-) cells, but it inhibited the adhesion of ECD (+) cells and promoted their migration. These results suggested that the migration and invasion of cancer cells may be enhanced by the reduction or loss of ECD.Using the same experimental system, we also assessed the effect of epidermal growth factor (EGF), which acts via the EGF receptor (EGFR), on the ECD-Ephi catenin intercellular adhesion system. 1) Aggregation assay : When the ECD (+) cellswere cultured on soft agar, they aggregated into balls. However, after the addition of EGF, … More the cells only formed small monolayred masses. When ECD (-) cells were cultured, they became fibroblast-like and addition of EGF had no effect. 2) alteration of ECD expression : ECD (+) cells showed strong ECD expression, confined to the cell membrane, but after the addition of EGF,ECD expression became widespread in the cells. 3)Invasion : When ECD (+) cells were cultured oncollagengel containing fibroblasts, they formed multilayredmasses. With the addition of EGF,they infiltrated into the gel. ECD (-) cells normally proliferated as monolayrs andinvaded into the gel, and these features were not changed bythe addition of EGF.4)Immunoblot analysis : ECD (+) cells were incubated with EGF and anti-ECD mAb (HECD-1) to produceimmunoprecipitation and the presence of phospho-tyrosine was invesigated. E catenin was converted into phosphotyrosine, suggesting that EGF-EGFR binding influencedthe cadoherin-catenin system and caused some abnormality of the intercellular adhesion mechanism. An immunohistochemicalinvestigation of human esophageal cancer tissue showed that lymph node metastasis occurred frequently with a poor prognosis in patients whose tumors exhibited reduced ECD orEphi-catenin expression.[Summary] Intercellular adhesion abnormalities, such as reduction of ECD orEphi catenin as wellas EGF-induced phospholyration of beta catenin, may contribute to invasion and metastasis of human esophageal cancer. Less