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CD44 Isoform Expression in Primary and Metastatic Pancreatic Adenocarcinoma¹

Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

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 [-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-assocaiated CD44 isoform.

¹ Supported in part by NIH Training Grant NIH DK 07191-20 (C. J. N. R.) and NIH Grant K08 CA01586-04 and NIH Grant NIDDK 43351 (A. K. R.).

² To whom correspondence should be addressed, at Gastrointestinal Unit Jackson 904, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114.

Received 2/ 6/95. Accepted 3/17/95.

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