DIFFERENTIAL EXPRESSION OF THE HYALURONAN RECEPTORS CD44 AND RHAMM INHUMAN PANCREATIC-CANCER CELLS

To explore the putative role of hyaluronan (HA) in tumor invasion in p ancreatic cancer, we investigated the expression of the HA receptors C D44s and RHAMM in a panel of human pancreatic cancer cell lines, Expre ssion of CD44s has been found in only 1 of 10 cell lines included in t his study, This cell line exhibits a highly differentiated phenotype w ithout any metastatic potential when injected into nude mice, Since it has previously been shown that normal pancreatic duct cells express a high level of CD44s, our results indicate that pancreatic cancer may be accompanied by an almost complete loss of CD44s expression, As demo nstrated by PCR amplification, this loss of CD44s expression is due to alternative splicing of CD44 pre-RNA, Although most of the pancreatic cancer cell lines express a complex but identical pattern of variant CD44 gene transcripts, only one higher molecular weight CD44 isoform c an be detected in a subset of pancreatic cancer cell lines in Western blot analysis, This variant CD44 molecule represents the epithelial CD 44 isoform (CD44v8-v10), When cells are cultured on Matrigel, the expr ession of additional CD44 variants is induced, suggesting that the ext racellular matrix can influence the expression of CD44 isoforms and th ereby may facilitate tumor invasion, This induction could be due to a regulatory process in the translation of the CD44 variant mRNAs expres sed in pancreatic tumor cells. Molecular cloning of a cDNA encoding hu man RHAMM reveals that both HA receptors are structurally unrelated, I n addition, they share an inverse expression pattern, RHAMM mRNA is ov erexpressed in pancreatic cancer cell lines exhibiting a poorly differ entiated phenotype and a high metastatic potential when injected into nude mice, These results indicate that CD44 and RHAMM differentially c ontribute to invasion of pancreatic adenocarcinoma; however, these fun ctions still remain to be determined.