Differential expression of the hyaluronan receptors CD44 and RHAMM in human pancreatic cancer cells.
To explore the putative role of hyaluronan (HA) in tumor invasion in pancreatic cancer, we investigated the expression of the HA receptors CD44s and RHAMM in a panel of human pancreatic cancer cell lines. Expression of CD44s has been found in only 1 of 10 cell lines included in this study. This cell line exhibits a highly differentiated phenotype without 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 demonstrated 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 can be detected in a subset of pancreatic cancer cell lines in Western blot analysis. This variant CD44 molecule represents the epithelial CD44 isoform (CD44v8-v10). When cells are cultured on Matrigel, the expression of additional CD44 variants is induced, suggesting that the extracellular matrix can influence the expression of CD44 isoforms and thereby may facilitate tumor invasion. This induction could be due to a regulatory process in the translation of the CD44 variant mRNAs expressed in pancreatic tumor cells. Molecular cloning of a cDNA encoding human RHAMM reveals that both HA receptors are structurally unrelated. In addition, they share an inverse expression pattern. RHAMM mRNA is overexpressed in pancreatic cancer cell lines exhibiting a poorly differentiated phenotype and a high metastatic potential when injected into nude mice. These results indicate that CD44 and RHAMM differentially contribute to invasion of pancreatic adenocarcinoma; however, these functions still remain to be determined.
Abetamann
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Department of Cell Biology and Cell Pathology, University of Marburg, Robert-Koch-Strasse 5, D-35033 Marburg, Germany.
Kern
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Elsässer
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D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C098946:hyaluronan-mediated motility receptor