Rall C J, Rustgi A K
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Cancer Res. 1995 May 1;55(9):1831-5.
CD44 is the transmembrane adhesion molecule which binds hyaluronate. The gene encoding CD44 is found on chromosome 11p and comprises 20 exons. Differential splicing of the 10 extracellular juxtamembranous exons (v1-10) generates the major isoforms of CD44. The major CD44 isoform found on hematopoetic cells (CD44s) contains none of the variably expressed exons, while the major isoform expressed on epithelial cells [CD44(v8-10)] contains exons v8-10. Metastasis-specific isoforms of CD44 were first documented in a model of rat pancreatic adenocarcinoma [CD44(v4-7), CD44(v6-7)] and subsequently in other cancers. This study is the first characterization of CD44 isoforms in primary and metastatic human pancreatic adenocarcinomas. CD44 isoforms were analyzed in specimens of 15 primary and 6 metastatic pancreatic adenocarcinomas as well as in 6 specimens of control pancreata by two different methods. Radiolabeled reverse transcriptase-PCR coupled with 8% PAGE allowed analysis of the major isoforms of CD44, while Southern blot hybridization with [alpha-32P]dCTP-labeled probes permitted analysis for metastasis-specific CD44 isoforms containing CD44(v6) or CD44(v8-10). No differences in the expression of CD44(v8-10) and CD44s were found among the primary and metastatic pancreatic adenocarcinomas, and control specimens of pancreata. However, a novel CD44(v6) isoform was found in metastatic lesions and may represent the human homologue of the rat pancreatic adenocarcinoma metastasis-associated CD44 isoform.
CD44是一种能结合透明质酸的跨膜黏附分子。编码CD44的基因位于11号染色体短臂上，由20个外显子组成。10个细胞外近膜外显子（v1 - 10）的可变剪接产生了CD44的主要异构体。造血细胞上发现的主要CD44异构体（CD44s）不包含任何可变表达的外显子，而上皮细胞上表达的主要异构体[CD44(v8 - 10)]包含外显子v8 - 10。CD44的转移特异性异构体最早在大鼠胰腺腺癌模型中被记录[CD44(v4 - 7)，CD44(v6 - 7)]，随后在其他癌症中也有发现。本研究首次对原发性和转移性人胰腺腺癌中的CD44异构体进行了特征描述。通过两种不同方法对15例原发性和6例转移性胰腺腺癌标本以及6例对照胰腺标本中的CD44异构体进行了分析。放射性标记的逆转录聚合酶链反应结合8%聚丙烯酰胺凝胶电泳可分析CD44的主要异构体，而用[α - 32P]dCTP标记的探针进行Southern印迹杂交可分析含有CD44(v6)或CD44(v8 - 10)的转移特异性CD44异构体。在原发性和转移性胰腺腺癌以及对照胰腺标本中，未发现CD44(v8 - 10)和CD44s表达的差异。然而，在转移灶中发现了一种新的CD44(v6)异构体，它可能代表大鼠胰腺腺癌转移相关CD44异构体的人类同源物。
