NO EVIDENCE FOR CANCER-RELATED CD44 SPLICE VARIANTS IN PRIMARY AND METASTATIC COLORECTAL-CANCER

The expression of alternatively spliced CD44 adhesion molecules has be en implicated in the pathogenesis and metastasis of colorectal cancer. Using a new set of primers for exon-specific reverse transcription-po lymerase chain reaction (RT-PCR) we delineated the exact exon composit ion of CD44 mRNAs in normal colorectal mucosa, including isolated colo nic crypts, in colorectal carcinomas and in their hepatic metastases. In addition, the surface expression of CD44 isoforms was analysed by i mmunohistochemistry. We identified by RT-PCR eight variant transcripts expressed in colorectal carcinomas and their metastases, but also con stitutively in normal colorectal epithelia. In the normal colorectal e pithelium, the surface expression of CD44 standard and variant molecul es was restricted to proliferating cells at the bottom of the crypts. Despite expression of these transcripts in colorectal cancers and thei r metastases, monoclonal antibodies specific for standard or variant e pitopes encoded by exons v5 and v6 stained only a few neoplastic lesio ns. These data point to a differentiation-specific CD44 expression and splicing pattern in proliferating colorectal epithelia. However, they do not support a cancer- or metastasis-specific CD44 splicing pattern . Instead, cell surface availability of CD44 epitopes was reduced rath er than increased in primary tumours and particularly in Liver metasta ses. (C) 1998 Elsevier Science Ltd. All rights reserved.