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表达，例如来自乳腺癌、肺癌、胃癌和结肠直肠癌的那些细胞系。CD44的剪接变异体在肿瘤的生长和转移中起重要作用。本研究通过北方印迹法检测60例结直肠癌组织中CD44剪接变异体外显子8 - 10的表达，发现其表达与结直肠癌的转移潜能有关。CD44变异体外显子8 - 10在肝转移癌中的表达水平显著高于无肝转移癌。此外，CD44变异体外显子8 - 10在肝转移癌中的表达高于原发性结直肠癌。我们已经建立了一种鼠单克隆抗体（mAb 44 - 1V）， ...更多信息 结果表明，分子量为130 kD的CD44v8 - 10在结直肠癌组织中表达，而在正常组织中不表达。我们使用该mAb 44 - 1V化学分析了结直肠癌中CD44变体外显子8至10产物的表达，并评估其预后价值。CD44v8 - 10的表达与淋巴结和血行转移密切相关。与CD44v8 - 10阴性肿瘤相比，CD44v8 - 10阳性肿瘤患者的死亡相对风险更大。多因素分析采用考克斯回归模型，CD44 v8 - 10表达是独立的预后指标。提示CD44v8 - 10在结直肠癌转移中起一定作用，CD44v8 - 10表达可能是一个具有预后意义的生物学指标。采用酶联免疫吸附试验（ELISA）检测可溶性CD44v8 - 10水平。我们报道了在免疫染色阳性的结直肠癌患者中血清CD44v8 - 10浓度的表达升高，表明其可作为结直肠癌患者血行转移的指标或预测因子。我们使用单克隆抗体44 - 10检测了CD44v8 - 10变体在人结肠癌细胞系HT 29转移中的作用。所有对照小鼠均发生了大量肝转移，而用mAb 44 - 1v预处理的组中仅1只小鼠（11.1%）发生了肝转移。然而，静脉内施用mAb 44 - 1V并不降低肝转移率。这些结果支持了CD44v8 - 10在原发癌迁移后的转移过程中起重要作用的假设，特别是在与远处器官毛细血管的粘附中。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