CD44 ISOFORM EXPRESSION IN PRIMARY AND METASTATIC PANCREATIC ADENOCARCINOMA

CD44 is the transmembrane adhesion molecule which binds hyaluronate. T he gene encoding CD44 is found on chromosome lip and comprises 20 exon s. 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 expr essed exons, while the major isoform expressed on epithelial cells [CD 44(v8-10)] contains exons v8-10. Metastasis-specific isoforms of CD44 were first documented in a model of rat pancreatic adenocarcinoma [CD4 4(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 speci mens of 15 primary and 6 metastatic pancreatic adenocarcinomas as well as in 6 specimens of control pancreata by two different methods. Radi olabeled reverse transcriptase-PCR coupled with 8% PAGE allowed analys is of the major isoforms of CD44, while Southern blot hybridization wi th [alpha-P-32]dCTP-labeled probes permitted analysis for metastasis-s pecific CD44 isoforms containing CD44(v6) or CD44(v8-10). No differenc es in the expression of CD44(v8-10) and CD44s were found among the pri mary and metastatic pancreatic adenocarcinomas, and control specimens of pancreata. However, a novel CD44(v6) isoform was found in metastati c lesions and may represent the human homologue of the rat pancreatic adenocarcinoma metastasis-associated CD44 isoform.