Finn L, Dougherty G, Finley G, Meisler A, Becich M, Cooper D L
Department of Pathology, University of Pittsburgh Medical School, PA 15261.
Biochem Biophys Res Commun. 1994 Apr 29;200(2):1015-22. doi: 10.1006/bbrc.1994.1551.
Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.
CD44分子的表达与人类和啮齿类动物肿瘤的生长及转移相关。在大鼠和小鼠肿瘤中表达的可变剪接变体已被证明可赋予非转移性癌细胞系转移潜能，并且大鼠变体mRNA序列的人类同源物在人类肿瘤中表达。在本研究中，通过定量逆转录聚合酶链反应（RT-PCR）检测了来自结肠癌及远处正常黏膜的配对RNA样本中的CD44表达。回顾性分析显示，与正常黏膜相比，结肠肿瘤细胞在CD44表达上存在数量和质量上的差异。这些差异包括：1）CD44转录本水平增加；2）可变剪接转录本水平增加；3）存在插入片段>400个碱基的更大可变剪接转录本；4）在所有病例的结肠腺癌中，主要的可变剪接CD44异构体是CD44R。有趣的是，根据可变型与标准CD44转录本的比例（R+V's/H），可以区分出两种CD44异构体表达模式，即“可变型主导”或“平衡”表达模式。对于表达先前与肿瘤转移相关的CD44可变外显子水平增加的肿瘤，提示预后不良。具体而言，无论Dukes分期如何，表达“可变型主导”表达模式的肿瘤患者以及两种模式的Dukes C期和D期肿瘤患者预后较差。
