Frequent expression of the high molecular, 673-bp CD44v3,v8-10 variant in colorectal adenomas and carcinomas.
CD44 is a transmembrane glycoprotein involved in the interaction between cells and the extracellular matrix. A large variety of alternatively spliced CD44 variants are expressed by different tumors with possible implication for tumor progression, formation of metastasis and survival. In colon carcinomas, previous reports described higher molecular bands of CD44 transcripts in neoplastic colonic tissue, although a complete analysis of multiple combinations of CD44v transcripts were not performed. We therefore analyzed the pattern of CD44 standard and variant (v2-v10) transcripts in colorectal adenomas and carcinomas by exon-specific RT-PCR amplification and sought CD44v transcripts specific for colonic neoplasias. Our data indicate that CD44 standard transcripts, including the epithelial form (C-v8,v9,v10-C) corresponding to a 720 bp transcript, were detected in 2/38 (5.2%) samples of normal mucosa, 20/20 (100%) adenomas and in 21/33 (63%) colorectal carcinomas. High molecular CD44v3,v8-10 (673 bp) transcripts were found in 2/33 (6%) samples from normal mucosa, 19/20 (95%) from adenomas and in 29/31 from colorectal carcinomas (93%). Similar CD44v3,v8-10 transcripts were detected in five from seven colorectal liver metastases, while normal liver did not contain high molecular CD44v3 variants. The same CD44v3,v8-10 (673 bp) variant was detected in HT-29 human colon carcinoma cells. Direct sequencing of the CD44v3 (673 bp) transcript in samples from colorectal carcinomas and HT-29 cells confirmed the assumed CD44v (-C-v3-v8-v9-v10-C-) cDNA sequence. Analysis of other CD44 variant transcripts (v4-v10) using exon specific primers were less frequently associated with colorectal neoplasias. These data report for the first time frequent expression of neoplasia-associated CD44v3,v8-10 variants in colorectal adenomas and carcinomas supporting the role of increased CD44 variant expression as an early event in colorectal carcinogenesis. The described CD44v3,v8-10 (673 bp) variant might be relevant for diagnosis and treatment of colorectal cancer.
Kopp
R
R
Department of Surgery, Klinikum Grosshadern, University of Munich, D-81377 Munich, Germany. r.kopp@khmh.de
Fichter
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Schalhorn
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Danescu
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Classen
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D000236:Adenoma / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics*; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger