Expression of variant CD44 in colorectal cancer and its relationship to metastasis

CD44的剪接变体在人类癌细胞系中过度表达，如乳腺癌、肺癌、胃癌和结直肠癌。人们认为CD44剪接变异体可能在肿瘤生长和转移中起重要作用。本研究旨在阐明人类结直肠癌中含有外显子8-10的CD44变体的表达与转移潜力之间的关系。我们发现，与匹配的正常结肠粘膜相比，在所有60例结直肠癌标本中，CD44剪接变体外显子8-10的表达均增加。CD44变异外显子8-10的表达水平在伴有肝转移的癌中明显高于无肝转移的癌。此外，CD44变异外显子8-10在肝转移癌中的表达比在原发性结直肠癌中的表达更强烈。我们已经建立了一种小鼠单克隆抗体（mAb 44-1V），该抗体与CD44变体外显子9产物中的epito…More pe反应，并证明分子量为130 kD的CD44v8-10在结直肠癌中表达，而在正常对应物中不表达。我们使用该mAb 44-1V免疫组织化学分析了CD44变体外显子8至10产物在结直肠癌中的表达，并评估其预后价值。CD44v8-10免疫反应性与淋巴结和血行转移均有显著相关性。cd44v8 -10阳性肿瘤患者的相对死亡风险高于cd44v8 -10阴性肿瘤患者。在Cox回归模型的多变量分析中，CD44v8-10表达成为独立的预后指标。这些结果提示CD44v8-10在结直肠癌的转移中发挥作用，CD44v8-10的表达可能是具有预后意义的生物学标志物。我们采用酶联免疫吸附试验（ELISA）系统检测可溶性CD44v8-10水平。我们报道，在免疫染色阳性的结直肠癌患者中，血清CD44v8-10浓度表达升高，提示其作为结直肠癌患者血行转移的指标或预测因子的有效性。此外，我们使用mAb 44-1V检测了变异CD44v8-10在人结肠癌细胞系HT29转移中的作用。所有对照小鼠都发生了大量的肝转移，而在mAb 44-1v预处理组中，只有一只小鼠（11.1%）发生了肝转移。然而，静脉注射mAb 44-1V并没有降低肝转移率。这些结果支持了CD44v8-10在原发肿瘤迁移后的转移过程中发挥重要作用的假设，特别是在粘附到远端器官的毛细血管中。少

Splice variants of CD44 are overexpressed in human cancer cell lines, such as those from breast, lung, stomach, and colorectal cancers. It is thought that splice variants of CD44 may play an important role in tumor growth and metastasis. This study was conducted to clarify the association between the expression of variant CD44 containing exons 8-10 and metastatic potential in human colorectal cancer.We found that the expression of a CD44 splice variant exons 8-10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colorectal mucosa, as determined by Northern blotting. The level of CD44 variant exon 8-10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variants exons 8-10 in liver metastases was more intense than that in the primary colorectal cancers. We have established a murine monoclonal antibody (mAb 44-1V) that is reactive with an epito … More pe in a CD44 variant exon 9 product, and demonstrated that CD44v8-10 with molecular weight of 130 kD was expressed in colorectal cancers, and not in normal counterparts. We analyzed the expression of the CD44 variant exon 8 to 10 product in colorectal cancer immunohistochemically using this mAb 44-1V,and evaluate its prognostic value. There were significant correlations between CD44v8-10 immunoreactivity and both lymph node and hematogenous metastasis. Patients with CD44v8-10-positive tumors had a greater relative risk of death compared with those tumors were CD44v8-10-negative. In multivariate analysis using Cox regression model, CD44v8-10 expression emerged as an independent prognostic indicator. These results suggested that CD44v8-10 plays a role in metastasis of colorectal cancer, and that CD44v8-10 expression may be a biologic marker of prognostic significance. We used an enzymed linked immunosorbent assay (ELISA) system to detect the soluble CD44v8-10 level. We report that the expression of serum CD44v8-10 concentration is elevated in colorectal cancer patients with positive immunostaining, suggesting its usefulness as an indicator or predictor of hematogenous metastasis in clorectal cancer patients.In addition, we examined the role of the variant CD44v8-10 in the metastasis of the human colon cancer cell line HT29 using mAb 44-1V.All of the control mice developed massive liver metastases, while only one mouse (11.1%) in the group pretreated with mAb 44-1v developed liver metastasis. However, the intravenous administration of mAb 44-1V did not reduce the rate of liver metastasis. These results support the hypothesis that CD44v8-10 plays an important role in the metastatic process after migration from the primary cancer, especially in the adhesion to the capillaries of distant organ. Less