Abstract
Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8–10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8–10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colorectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8–10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8–10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8–10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8–10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.
Keywords: Liver metastasis, Colorectal cancer, CD44 variant exons8–10, Adhesion molecule
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REFERENCES
- 1).Hart , I. R. , Goode , N. T. and Wilson , R. E.Molecular aspects of the metastatic cascade . Biochim. Biophys. Acta , 989 , 65 – 84 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 2).Mac Carthy , J. B. , Basara , M. L. , Palm , S. L. , Sas , D. F. and Furcht , L. T.The role of cell‐adhesion proteins—laminin and fibronectin—in the movement of malignant and metastatic cells . Cancer Metastasis Rev. , 4 , 99 – 106 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 3).Liotta , L. A. and Stetler‐Stevenson , W. G.Metallopro‐teinaseand cancer invasion . Semin, Cancer Biol , 1 , 99 – 106 ( 1990. ). [PubMed] [Google Scholar]
- 4).Jalkanen , S. , Bargatze , R. F. , Herron , L. R. and Butcher , E. C.A lymphoid cell surface protein involved in endo‐thelial cell recognition and lymphocyte homing in man . Eur. J. Immunol , 16 , 1195 – 1202 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5).Jalkanen , S. , Nakache , M. and Butcher , E. C.Homing receptors and the control oflymphocyte migration . Immunol. Rev. , 91 , 39 – 60 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 6).Iderda , R. L. , Carter , W. G. , Nottenburg , C. , Wayner , E. A. , Gallatin , W. M. and St. John , T.Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion receptor for high endothelium . Proc. Natl. Acad. Sci. USA , 86 , 4659 – 4663 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7).Picker , L. J. , Nakache , M. and Butcher , E. C.Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types . J. Cell Biol. , 109 , 927 – 937 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8).Gallatin , W. M. , Wayner , E. A. , Hoffman , P. A. , St. John , T. , Butcher , E. C. and Carter , W. G.Structural homology between lymphocyte receptors for high endothelium and class III extracellular matrix receptor . Proc. Natl. Acad. Sci. USA , 86 , 4654 – 4658 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9).Wayner , E. A. , Carter , W. G. , Piotrowicz , R. S. and Kunicki , T. J.The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic‐IIa . J. Cell Biol. , 107 , 1881 – 1891 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10).Stamenkovic , I. , Aruffo , A. , Amiot , M. and Seed , B.The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate‐bearing cells . EMBO J. , 10 , 343 – 348 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11).Jalkanen , S. and Jalkanen , M.Lymphocyte CD44 binds the COOH‐terminal heparin‐bindings domain of fibronectin . J. Cell Biol. , 116 , 817 – 825 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12).Hofmann , M. , Rudy , W. , Zöller , M. , Tölg , C. , Ponta , H. , Herrlich , P. and Günthert , U.CD44 splice variant confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines . Cancer Res. , 51 , 5292 – 5297 ( 1991. ). [PubMed] [Google Scholar]
- 13).Günthert , U. , Hofmann , M. , Rudy , W. , Reber , S. , Zöller , M. , Haußmann , I. , Matzku , S. , Wenzel , A. , Ponta , H. and Herrlich , P.A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells . Cell , 65 , 13 – 24 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 14).Jackson , D. G. , Buckley , J. and Bell , J. I.Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain . J. Biol. Chem. , 267 , 4732 – 4739 ( 1992. ). [PubMed] [Google Scholar]
- 15).Screaton , G. R. , Bell , M. V. , Jackson , D. G. , Cornelis , F. B. , Gerth , U. and Bell , J. I.Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons . Proc. Natl. Acad. Sci. USA , 89 , 12160 – 12164 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16).Rudy , W. , Hofmann , M. , Schwartz‐Albiez , R. , Zöller , M. , Heider , K.‐H. , Ponta , H. and Herrlich , P.The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior . Cancer Res. , 53 , 1262 – 1268 ( 1993. ). [PubMed] [Google Scholar]
- 17).Nemec , R. E. , Toole , B. P. and Kundson , W.The cell surface hyaluronate binding sites of invasive human bladder carcinoma cells . Biochem. Biophys. Res. Commun. , 149 , 249 – 257 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 18).Chomczynski , P. and Sacchi , N.Single‐step method of RNA isolation by acid guanidinium thiocyanate‐phenol‐chloroform extraction . Anal. Biochem. , 162 , 156 – 159 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 19).Matsumura , Y. and Tarin , D.Significance of CD44 gene products for cancer diagnosis and disease evaluation . Lancet , 340 , 1053 – 1058 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 20).Heider , K.‐H. , Hofmann , M. , Hors , E. , van den Berg , F. , Ponta , H. , Herrlich , P. and Pals , S. T.A human homo‐logue of the rat metastasis‐associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps . J. Cell Biol. , 120 , 227 – 233 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21).Tanabe , K. K. , Ellis , L. M. and Saya , H.Expression of CD44R1 adhesion molecule in colon carcinomas and metastases . Lancet , 341 , 725 – 726 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 22).Guo , Y. J. , Liu , G. , Wang , X. , Jin , D. , Wu , M. , Ma , J. and Sy , M.‐S.Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer . Cancer Res. , 54 , 422 – 426 ( 1994. ). [PubMed] [Google Scholar]
- 23).Wielenga , V. J. M. , Heider , K.‐H. , Offerhaus , G. J. A. , Adolf , G. R. , van den Berg , F. M. , Ponta , H. , Herrlich , P. and Pals , S. T.Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression . Cancer Res. , 53 , 4754 – 4756 ( 1993. ). [PubMed] [Google Scholar]
- 24).Mayer , B. , Jauch , K. W. , Günthert , U. , Figdor , C. G. , Schildberg , F. W. , Funbe , I. and Johnson , J. P.De‐novo expression of CD44 and survival in gastric cancer . Lancet , 342 , 1019 – 1022 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 25).Seiter , B. S. , Arch , R. , Reber , S. , Komitowski , D. , Hofmann , M. , Ponta , H. , Herrlich , P. , Matzku , S. and Zöller , M.Prevention of tumor metastasis formation by anti‐variant CD44 . J. Exp. Med. , 177 , 443 – 455 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26).Arch , R. , Wirth , K. , Hofmann , M. , Ponta , H. , Matzku , S. , Herrlich , P. and Zöller , M.Participation in normal immune responses of a metastasis‐inducing splice variant of CD44 . Science , 257 , 682 – 685 ( 1992. ). [DOI] [PubMed] [Google Scholar]