EXPRESSION OF ALTERNATIVELY SPLICED FORMS OF THE CD44 EXTRACELLULAR-MATRIX RECEPTOR ON HUMAN LUNG CARCINOMAS

Expression of isoforms of the CD44 hyaluronan receptor/lymph-node endo thelial receptor by human tumour cells is thought to play a role in tu mour growth and metastasis. These isoforms which vary in the length of the extracellular domain are generated by differential RNA splicing t hat involves the 10 alternative exons (v1 to v10) encoding the membran e proximal region of the molecule. Several tumours have been shown to over-express CD44 containing the v6 exon, and this, together with over evidence, has led to the suggestion that v6 may play a causative role in tumour metastasis. In this report we have compared the expression of CD44 isoforms between different lung tumour lines, including SCLC, squamous-cell carcinoma, adenocarcinoma and mesothelioma, using both R T-PCR and fluorescent antibody staining with a panel of CD44 exon-spec ific monoclonal antibodies (MABs). Our results show large differences in vCD44 expression between individual tumour lines. Little or no vCD4 4 containing the metastasis-associated v6 exon was detected in most tu mours, including the highly metastatic SCLC lines. Indeed, the SCLC li nes and some squamous-cell carcinomas contained only very low levels o f either vCD44 or CD44H, indicating that CD44 expression may not alway s correlate with tumour development or dissemination. One of the squam ous-cell carcinomas studied (HOTZ) was found to express a complex mixt ure of CD44 splice variants similar to the immortalized normal bronchi al epithelial line BEAS-2B. Cloning several splice variants that have also been identified on leukaemic cells, normal keratinocytes and acti vated peripheral-blood lymphocytes. (C) 1994 Wiley-Liss, Inc.