Herrlich P, Pals S, Ponta H
Forschungszentrum Karlsruhe, Institut für Genetik, Germany.
Eur J Cancer. 1995 Jul-Aug;31A(7-8):1110-2. doi: 10.1016/0959-8049(95)00252-e.
Alternative splicing of ten different variant exons (v1-v10) is responsible for the creation of a large number of different CD44 surface proteins. Some of these proteins play decisive roles in the metastatic spread of rat tumours. Also in human cancers, CD44 splice variants are frequently expressed in advanced states of tumorigenesis. In breast cancer and in non-Hodgkin's lymphomas expression of exon v6 is correlated with poor prognosis of patient survival. In colorectal carcinogenesis, expression of exon v5 is an early tumour marker since it is already detectable on small dysplastic polyps (but not on normal colon epithelium). In contrast, exon v6 expression occurred with increased frequency with tumour progression, and its expression on colorectal tumours indicated reduced survival probability. Most likely, tumours carrying the CD44 v6 epitope acquire selective advantage during tumour progression and metastasis formation. This could be a proliferative advantage since mice transgenic for the CD44 isoform CD44v4-v7 on T lymphocytes show an accelerated T-dependent immune response as compared with non-transgenic siblings.
十种不同可变外显子（v1 - v10）的可变剪接导致了大量不同的CD44表面蛋白的产生。其中一些蛋白在大鼠肿瘤的转移扩散中起决定性作用。在人类癌症中，CD44剪接变体也常在肿瘤发生的晚期阶段表达。在乳腺癌和非霍奇金淋巴瘤中，外显子v6的表达与患者生存预后不良相关。在结直肠癌发生过程中，外显子v5的表达是一种早期肿瘤标志物，因为在小的发育异常息肉上就已经可以检测到（但在正常结肠上皮上检测不到）。相反，外显子v6的表达随着肿瘤进展而频率增加，其在结直肠癌上的表达表明生存概率降低。最有可能的是，携带CD44 v6表位的肿瘤在肿瘤进展和转移形成过程中获得了选择性优势。这可能是一种增殖优势，因为在T淋巴细胞上携带CD44同种型CD44v4 - v7的转基因小鼠与非转基因同胞相比，表现出加速的T细胞依赖性免疫反应。
