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Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts.

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Affiliations

  • 1. McGill Cancer Centre, Biochemistry Department, McGill University, Montreal, Quebec, Canada.
      Authors
    • Eidelman FJ 1
    (1 author)

The Journal of Cell Biology, 01 Oct 1993, 123(2):467-475
https://doi.org/10.1083/jcb.123.2.467 PMID: 8408226 PMCID: PMC2119830

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Abstract 

Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpressed in many carcinomas. CEA has been shown to function in vitro as a homotypic intercellular adhesion molecule. This correlation of overproduction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation. Using stable CEA transfectants of the rat L6 myoblast cell line as a model system of differentiation, we show that fusion into myotubes and, in fact, the entire molecular program of differentiation, including creatine phosphokinase upregulation, myogenin upregulation, and beta-actin downregulation are completely abrogated by the ectopic expression of CEA. The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage. The adhesion function of CEA is essential for this effect since an adhesion-defective N domain deletion mutant of CEA was ineffective in blocking fusion and CEA transfectants treated with adhesion-blocking peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose division potential with differentiation similarly to the parental cell line. Thus the expression of functional CEA on the surface of cells can block terminal differentiation and maintain proliferative potential.

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J Cell Biol. 1993 Oct 2; 123(2): 467–475.
PMCID: PMC2119830
PMID: 8408226

Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts

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Abstract

Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpressed in many carcinomas. CEA has been shown to function in vitro as a homotypic intercellular adhesion molecule. This correlation of overproduction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation. Using stable CEA transfectants of the rat L6 myoblast cell line as a model system of differentiation, we show that fusion into myotubes and, in fact, the entire molecular program of differentiation, including creatine phosphokinase upregulation, myogenin upregulation, and beta- actin downregulation are completely abrogated by the ectopic expression of CEA. The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage. The adhesion function of CEA is essential for this effect since an adhesion-defective N domain deletion mutant of CEA was ineffective in blocking fusion and CEA transfectants treated with adhesion-blocking peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose division potential with differentiation similarly to the parental cell line. Thus the expression of functional CEA on the surface of cells can block terminal differentiation and maintain proliferative potential.

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Selected References

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  • Abbasi AM, Chester KA, MacPherson AJ, Boxer GM, Begent RH, Malcolm AD. Localization of CEA messenger RNA by in situ hybridization in normal colonic mucosa and colorectal adenocarcinomas. J Pathol. 1992 Dec;168(4):405–411. [Abstract] [Google Scholar]
  • Afar DE, Stanners CP, Bell JC. Tyrosine phosphorylation of biliary glycoprotein, a cell adhesion molecule related to carcinoembryonic antigen. Biochim Biophys Acta. 1992 Feb 19;1134(1):46–52. [Abstract] [Google Scholar]
  • Beauchemin N, Benchimol S, Cournoyer D, Fuks A, Stanners CP. Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. Mol Cell Biol. 1987 Sep;7(9):3221–3230. [Europe PMC free article] [Abstract] [Google Scholar]
  • Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989 Apr 21;57(2):327–334. [Abstract] [Google Scholar]
  • Boucher D, Cournoyer D, Stanners CP, Fuks A. Studies on the control of gene expression of the carcinoembryonic antigen family in human tissue. Cancer Res. 1989 Feb 15;49(4):847–852. [Abstract] [Google Scholar]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [Abstract] [Google Scholar]
  • Cournoyer D, Beauchemin N, Boucher D, Benchimol S, Fuks A, Stanners CP. Transcription of genes of the carcinoembryonic antigen family in malignant and nonmalignant human tissues. Cancer Res. 1988 Jun 1;48(11):3153–3157. [Abstract] [Google Scholar]
  • Den H, Malinzak DA, Keating HJ, Rosenberg A. Influence of Concanavalin A, wheat germ agglutinin, and soybean agglutinin on the fusion of myoblasts in vitro. J Cell Biol. 1975 Dec;67(3):826–834. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dickson G, Peck D, Moore SE, Barton CH, Walsh FS. Enhanced myogenesis in NCAM-transfected mouse myoblasts. Nature. 1990 Mar 22;344(6264):348–351. [Abstract] [Google Scholar]
  • Edelman GM. Cell adhesion and morphogenesis: the regulator hypothesis. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1460–1464. [Europe PMC free article] [Abstract] [Google Scholar]
  • Edelman GM. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol. 1986;2:81–116. [Abstract] [Google Scholar]
  • Endo T, Nadal-Ginard B. Three types of muscle-specific gene expression in fusion-blocked rat skeletal muscle cells: translational control in EGTA-treated cells. Cell. 1987 May 22;49(4):515–526. [Abstract] [Google Scholar]
  • Florini JR, Roberts AB, Ewton DZ, Falen SL, Flanders KC, Sporn MB. Transforming growth factor-beta. A very potent inhibitor of myoblast differentiation, identical to the differentiation inhibitor secreted by Buffalo rat liver cells. J Biol Chem. 1986 Dec 15;261(35):16509–16513. [Abstract] [Google Scholar]
  • Fujimori T, Miyatani S, Takeichi M. Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos. Development. 1990 Sep;110(1):97–104. [Abstract] [Google Scholar]
  • Gilfix BM, Sanwal BD. Inhibition of myoblast fusion by tunicamycin and pantomycin. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1184–1191. [Abstract] [Google Scholar]
  • GOLD P, FREEDMAN SO. DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES. J Exp Med. 1965 Mar 1;121:439–462. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gossett LA, Zhang W, Olson EN. Dexamethasone-dependent inhibition of differentiation of C2 myoblasts bearing steroid-inducible N-ras oncogenes. J Cell Biol. 1988 Jun;106(6):2127–2137. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V, Nadal-Ginard B. Interaction of myogenic factors and the retinoblastoma protein mediates muscle cell commitment and differentiation. Cell. 1993 Feb 12;72(3):309–324. [Abstract] [Google Scholar]
  • Hass GM, Bolling TJ, Kinders RJ, Henslee JG, Mandecki W, Dorwin SA, Shively JE. Preparation of synthetic polypeptide domains of carcinoembryonic antigen and their use in epitope mapping. Cancer Res. 1991 Apr 1;51(7):1876–1882. [Abstract] [Google Scholar]
  • Hatta K, Takagi S, Fujisawa H, Takeichi M. Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. Dev Biol. 1987 Mar;120(1):215–227. [Abstract] [Google Scholar]
  • Higashide T, Hinoda Y, Itoh J, Takahashi H, Satoh Y, Ibayashi Y, Imai K, Yachi A. Detection of mRNAs of carcinoembryonic antigen and nonspecific cross-reacting antigen genes in colorectal adenomas and carcinomas by in situ hybridization. Jpn J Cancer Res. 1990 Nov;81(11):1149–1154. [Europe PMC free article] [Abstract] [Google Scholar]
  • Holland PC, Pena SD, Guerin CW. Developmental regulation of neuraminidase-sensitive lectin-binding glycoproteins during myogenesis of rat L6 myoblasts. Biochem J. 1984 Mar 1;218(2):465–473. [Europe PMC free article] [Abstract] [Google Scholar]
  • Holland PC, Herscovics A. Inhibition of myoblast fusion by the glucosidase inhibitor N-methyl-1-deoxynojirimycin, but not by the mannosidase inhibitor 1-deoxymannojirimycin. Biochem J. 1986 Sep 1;238(2):335–340. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kaufman SJ, Parks CM. Loss of growth control and differentiation in the fu-1 variant of the L8 line of rat myoblasts. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3888–3892. [Europe PMC free article] [Abstract] [Google Scholar]
  • Knudsen KA, Myers L, McElwee SA. A role for the Ca2(+)-dependent adhesion molecule, N-cadherin, in myoblast interaction during myogenesis. Exp Cell Res. 1990 Jun;188(2):175–184. [Abstract] [Google Scholar]
  • Lathrop B, Olson E, Glaser L. Control by fibroblast growth factor of differentiation in the BC3H1 muscle cell line. J Cell Biol. 1985 May;100(5):1540–1547. [Europe PMC free article] [Abstract] [Google Scholar]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [Abstract] [Google Scholar]
  • Linkhart TA, Clegg CH, Hauschka SD. Control of mouse myoblast commitment to terminal differentiation by mitogens. J Supramol Struct. 1980;14(4):483–498. [Abstract] [Google Scholar]
  • Oikawa S, Inuzuka C, Kuroki M, Arakawa F, Matsuoka Y, Kosaki G, Nakazato H. A specific heterotypic cell adhesion activity between members of carcinoembryonic antigen family, W272 and NCA, is mediated by N-domains. J Biol Chem. 1991 May 5;266(13):7995–8001. [Abstract] [Google Scholar]
  • Okazaki K, Holtzer H. Myogenesis: fusion, myosin synthesis, and the mitotic cycle. Proc Natl Acad Sci U S A. 1966 Nov;56(5):1484–1490. [Europe PMC free article] [Abstract] [Google Scholar]
  • Olson EN, Caldwell KL, Gordon JI, Glaser L. Regulation of creatine phosphokinase expression during differentiation of BC3H1 cells. J Biol Chem. 1983 Feb 25;258(4):2644–2652. [Abstract] [Google Scholar]
  • Olson EN, Spizz G, Tainsky MA. The oncogenic forms of N-ras or H-ras prevent skeletal myoblast differentiation. Mol Cell Biol. 1987 Jun;7(6):2104–2111. [Europe PMC free article] [Abstract] [Google Scholar]
  • Parfett CL, Jamieson JC, Wright JA. Changes in cell surface glycoproteins on non-differentiating L6 rat myoblasts selected for resistance to concanavalin A. Exp Cell Res. 1983 Apr 1;144(2):405–415. [Abstract] [Google Scholar]
  • Paxton RJ, Mooser G, Pande H, Lee TD, Shively JE. Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family. Proc Natl Acad Sci U S A. 1987 Feb;84(4):920–924. [Europe PMC free article] [Abstract] [Google Scholar]
  • Payne PA, Olson EN, Hsiau P, Roberts R, Perryman MB, Schneider MD. An activated c-Ha-ras allele blocks the induction of muscle-specific genes whose expression is contingent on mitogen withdrawal. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8956–8960. [Europe PMC free article] [Abstract] [Google Scholar]
  • Pinset C, Whalen RG. Manipulation of medium conditions and differentiation in the rat myogenic cell line L6. Dev Biol. 1984 Apr;102(2):269–277. [Abstract] [Google Scholar]
  • Pouliot Y, Holland PC, Blaschuk OW. Developmental regulation of a cadherin during the differentiation of skeletal myoblasts. Dev Biol. 1990 Oct;141(2):292–298. [Abstract] [Google Scholar]
  • Rahm M, Jin P, Sümegi J, Sejersen T. Elevated c-fos expression inhibits differentiation of L6 rat myoblasts. J Cell Physiol. 1989 May;139(2):237–244. [Abstract] [Google Scholar]
  • Richler C, Yaffe D. The in vitro cultivation and differentiation capacities of myogenic cell lines. Dev Biol. 1970 Sep;23(1):1–22. [Abstract] [Google Scholar]
  • Rutishauser U, Acheson A, Hall AK, Mann DM, Sunshine J. The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science. 1988 Apr 1;240(4848):53–57. [Abstract] [Google Scholar]
  • Shuster J, Thomson DM, Fuks A, Gold P. Immunologic approaches to diagnosis of malignancy. Prog Exp Tumor Res. 1980;25:89–139. [Abstract] [Google Scholar]
  • Spearman MA, Jamieson JC, Wright JA. Studies on the effect of glycoprotein processing inhibitors on fusion of L6 myoblast cell lines. Exp Cell Res. 1987 Jan;168(1):116–126. [Abstract] [Google Scholar]
  • Stanners CP, Eliceiri GL, Green H. Two types of ribosome in mouse-hamster hybrid cells. Nat New Biol. 1971 Mar 10;230(10):52–54. [Abstract] [Google Scholar]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [Europe PMC free article] [Abstract] [Google Scholar]
  • Terry WD, Henkart PA, Coligan JE, Todd CW. Carcinoembryonic antigen: characterization and clinical applications. Transplant Rev. 1974;20(0):100–129. [Abstract] [Google Scholar]
  • Wakelam MJ. The fusion of myoblasts. Biochem J. 1985 May 15;228(1):1–12. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wright WE, Sassoon DA, Lin VK. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989 Feb 24;56(4):607–617. [Abstract] [Google Scholar]
  • Yaffe D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci U S A. 1968 Oct;61(2):477–483. [Europe PMC free article] [Abstract] [Google Scholar]
  • Zimmermann W, Weber B, Ortlieb B, Rudert F, Schempp W, Fiebig HH, Shively JE, von Kleist S, Thompson JA. Chromosomal localization of the carcinoembryonic antigen gene family and differential expression in various tumors. Cancer Res. 1988 May 1;48(9):2550–2554. [Abstract] [Google Scholar]
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