DIFFERENTIAL EXPRESSION OF THE HUMAN METASTASIS ADHESION MOLECULE CD44V IN NORMAL AND CARCINOMATOUS STOMACH MUCOSA OF CHINESE SUBJECTS

Background. CD44 is a cell surface adhesion molecule involved in cell- cell and cell-matrix interactions. Tumor cells transfected to overexpr ess the isoform CD44V readily gain access to lymph nodes and form dist ant metastases. Methods. Monoclonal antibodies directed at epitopes co mmon to known CD44 isoforms were used to investigate CD44V expression in 30 normal gastric mucosa tissues, 64 different gastric adenocarcino mas, 20 metastatic adenocarcinoma lymph nodes and 4 established gastri c carcinoma cell lines. In addition, CD44V gene expression in six gast ric adenocarcinoma tissues and four gastric cancer cell lines were inv estigated by northern blotting. Results. Immunohistochemistry screenin g of 30 subjects with normal gastric mucosa did not reveal expression of CD44 variants. Areas of intestinal metaplasia, a precancerous lesio n, were stained with antibodies against either V5- or V6-containing is oforms of CD44. Tubular and signet-ring cell types of adenocarcinoma w ere strongly positive for epitopes encoded by CD44 variants containing exons V5 (41/49 and 10/10, respectively). Some tubular type adenocarc inomas (15/49) also expressed CD44 variants containing the V6 epitope. Tumor differentiation was closely related to CD44 V5 expression (P < 0.001). In addition, 18 of 20 gastric adenocarcinomas metastatic to ly mph nodes expressed the V5 epitope of CD44 and 4 of 20 expressed the V 6 epitope. Analysis of four established gastric adenocarcinoma cell li nes revealed that two had moderate to strong expression of exons V5 an d V6 of CD44. An antibody directed against CD44 variants containing ex ons V8 to V10 strongly stained all gastric adenocarcinoma cell lines. Northern blotting demonstrated that all four tumor cell lines and six gastric carcinoma mucosa tissues expressed CD44V. Conclusions. Generat ion of CD44 splice variants may be closely linked with gastric carcino ma tumorigenesis and differentiation. In addition, expression of CD44 variants containing exons V5 and V6 may be used as an indicator of evo lving gastric cancer.