Abstract
Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface, the crypts, and the glandular lumina. In poorly differentiated adenocarcinomas, labeling also is observed at the interface between cancer tissue and stroma, or in clumps of malignant cells, forming a pattern that highlights the presence of small, compressed lumina. The cingulin content of four adenocarcinomas, estimated by immunoblotting and densitometry, was higher than that of the normal tissue (150% to 230%). Cingulin was detected in a metastasis from a colon adenocarcinoma but not in nonepithelial tissues and neoplasias, suggesting that cingulin may be a useful marker in the characterization of colonic and probably other epithelial neoplasias.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ABERCROMBIE M., AMBROSE E. J. The surface properties of cancer cells: a review. Cancer Res. 1962 Jun;22:525–548. [PubMed] [Google Scholar]
- Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
- Carboni J. M., Howe C. L., West A. B., Barwick K. W., Mooseker M. S., Morrow J. S. Characterization of intestinal brush border cytoskeletal proteins of normal and neoplastic human epithelial cells. A comparison with the avian brush border. Am J Pathol. 1987 Dec;129(3):589–600. [PMC free article] [PubMed] [Google Scholar]
- Chantret I., Barbat A., Dussaulx E., Brattain M. G., Zweibaum A. Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. Cancer Res. 1988 Apr 1;48(7):1936–1942. [PubMed] [Google Scholar]
- Citi S., Kendrick-Jones J. Regulation in vitro of brush border myosin by light chain phosphorylation. J Mol Biol. 1986 Apr 5;188(3):369–382. doi: 10.1016/0022-2836(86)90161-0. [DOI] [PubMed] [Google Scholar]
- Citi S., Kendrick-Jones J. Studies on the structure and conformation of brush border myosin using monoclonal antibodies. Eur J Biochem. 1987 Jun 1;165(2):315–325. doi: 10.1111/j.1432-1033.1987.tb11444.x. [DOI] [PubMed] [Google Scholar]
- Citi S., Sabanay H., Jakes R., Geiger B., Kendrick-Jones J. Cingulin, a new peripheral component of tight junctions. Nature. 1988 May 19;333(6170):272–276. doi: 10.1038/333272a0. [DOI] [PubMed] [Google Scholar]
- Citi S., Sabanay H., Kendrick-Jones J., Geiger B. Cingulin: characterization and localization. J Cell Sci. 1989 May;93(Pt 1):107–122. doi: 10.1242/jcs.93.1.107. [DOI] [PubMed] [Google Scholar]
- DUKES C. E., BUSSEY H. J. The spread of rectal cancer and its effect on prognosis. Br J Cancer. 1958 Sep;12(3):309–320. doi: 10.1038/bjc.1958.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FARQUHAR M. G., PALADE G. E. Junctional complexes in various epithelia. J Cell Biol. 1963 May;17:375–412. doi: 10.1083/jcb.17.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friend D. S., Gilula N. B. Variations in tight and gap junctions in mammalian tissues. J Cell Biol. 1972 Jun;53(3):758–776. doi: 10.1083/jcb.53.3.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukamachi H., Mizuno T., Kim Y. S. Gland formation of human colon cancer cells combined with foetal rat mesenchyme in organ culture: an ultrastructural study. J Cell Sci. 1987 Jun;87(Pt 5):615–621. doi: 10.1242/jcs.87.5.615. [DOI] [PubMed] [Google Scholar]
- Fulker M. J., Cooper E. H., Tanaka T. Proliferation and ultrastructure of papillary transitional cell carcinoma of the human bladder. Cancer. 1971 Jan;27(1):71–82. doi: 10.1002/1097-0142(197101)27:1<71::aid-cncr2820270112>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Goodenough D. A., Revel J. P. A fine structural analysis of intercellular junctions in the mouse liver. J Cell Biol. 1970 May;45(2):272–290. doi: 10.1083/jcb.45.2.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gumbiner B. Structure, biochemistry, and assembly of epithelial tight junctions. Am J Physiol. 1987 Dec;253(6 Pt 1):C749–C758. doi: 10.1152/ajpcell.1987.253.6.C749. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Loewenstein W. R. Junctional intercellular communication and the control of growth. Biochim Biophys Acta. 1979 Feb 4;560(1):1–65. doi: 10.1016/0304-419x(79)90002-7. [DOI] [PubMed] [Google Scholar]
- Martinez-Palomo A., Braislovsky C., Bernhard W. Ultrastructural modifications of the cell surface and intercellular contacts of some transformed cell strains. Cancer Res. 1969 Apr;29(4):925–937. [PubMed] [Google Scholar]
- Martínez-Palomo A. Ultrastructural modifications of intercellular junctions in some epithelial tumors. Lab Invest. 1970 Jun;22(6):605–614. [PubMed] [Google Scholar]
- Matsudaira P. T., Burgess D. R. SDS microslab linear gradient polyacrylamide gel electrophoresis. Anal Biochem. 1978 Jul 1;87(2):386–396. doi: 10.1016/0003-2697(78)90688-7. [DOI] [PubMed] [Google Scholar]
- Merk F. B., Pauli B. U., Jacobs J. B., Alroy J., Friedell G. H., Weinstein R. S. Malignant transformation of urinary bladder in humans and in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-exposed Fischer rats: ultrastructure of the major components of the permeability barrier. Cancer Res. 1977 Aug;37(8 Pt 2):2843–2853. [PubMed] [Google Scholar]
- Moll R., Cowin P., Kapprell H. P., Franke W. W. Desmosomal proteins: new markers for identification and classification of tumors. Lab Invest. 1986 Jan;54(1):4–25. [PubMed] [Google Scholar]
- Mullin J. M., O'Brien T. G. Effects of tumor promoters on LLC-PK1 renal epithelial tight junctions and transepithelial fluxes. Am J Physiol. 1986 Oct;251(4 Pt 1):C597–C602. doi: 10.1152/ajpcell.1986.251.4.C597. [DOI] [PubMed] [Google Scholar]
- Nicolson G. L., Dulski K. M., Trosko J. E. Loss of intercellular junctional communication correlates with metastatic potential in mammary adenocarcinoma cells. Proc Natl Acad Sci U S A. 1988 Jan;85(2):473–476. doi: 10.1073/pnas.85.2.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ojakian G. K. Tumor promoter-induced changes in the permeability of epithelial cell tight junctions. Cell. 1981 Jan;23(1):95–103. doi: 10.1016/0092-8674(81)90274-9. [DOI] [PubMed] [Google Scholar]
- Pauli B. U., Weinstein R. S. Correlations between cell surface protease activities and abnormalities of occludens junctions in rat bladder carcinoma in vitro. Cancer Res. 1982 Jun;42(6):2289–2297. [PubMed] [Google Scholar]
- Pickett P. B., Pitelka D. R., Hamamoto S. T., Misfeldt D. S. Occluding junctions and cell behavior in primary cultures of normal and neoplastic mammary gland cells. J Cell Biol. 1975 Aug;66(2):316–332. doi: 10.1083/jcb.66.2.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pitelka D. R., Hamamoto S. T., Taggart B. N. Epithelial cell junctions in primary and metastatic mammary tumors of mice. Cancer Res. 1980 May;40(5):1588–1599. [PubMed] [Google Scholar]
- Quinonez G., Simon G. T. Cellular junctions in a spectrum of human malignant tumors. Ultrastruct Pathol. 1988;12(4):389–405. doi: 10.3109/01913128809064209. [DOI] [PubMed] [Google Scholar]
- Robine S., Huet C., Moll R., Sahuquillo-Merino C., Coudrier E., Zweibaum A., Louvard D. Can villin be used to identify malignant and undifferentiated normal digestive epithelial cells? Proc Natl Acad Sci U S A. 1985 Dec;82(24):8488–8492. doi: 10.1073/pnas.82.24.8488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staehelin L. A. Structure and function of intercellular junctions. Int Rev Cytol. 1974;39:191–283. doi: 10.1016/s0074-7696(08)60940-7. [DOI] [PubMed] [Google Scholar]
- Stevenson B. R., Anderson J. M., Goodenough D. A., Mooseker M. S. Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. J Cell Biol. 1988 Dec;107(6 Pt 1):2401–2408. doi: 10.1083/jcb.107.6.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevenson B. R., Siliciano J. D., Mooseker M. S., Goodenough D. A. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol. 1986 Sep;103(3):755–766. doi: 10.1083/jcb.103.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi T., Iwama N. Architectural pattern of gastric adenocarcinoma--a 3-dimensional reconstruction study. Virchows Arch A Pathol Anat Histopathol. 1984;403(2):127–134. doi: 10.1007/BF00695229. [DOI] [PubMed] [Google Scholar]
- Weinstein R. S., Merk F. B., Alroy J. The structure and function of intercellular junctions in cancer. Adv Cancer Res. 1976;23:23–89. doi: 10.1016/s0065-230x(08)60543-6. [DOI] [PubMed] [Google Scholar]
- Weinstein R. S., Pauli B. U. Cell junctions and the biological behaviour of cancer. Ciba Found Symp. 1987;125:240–260. doi: 10.1002/9780470513408.ch14. [DOI] [PubMed] [Google Scholar]
- West A. B., Isaac C. A., Carboni J. M., Morrow J. S., Mooseker M. S., Barwick K. W. Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms. Gastroenterology. 1988 Feb;94(2):343–352. doi: 10.1016/0016-5085(88)90421-0. [DOI] [PubMed] [Google Scholar]
- Younes M., Harris A. S., Morrow J. S. Fodrin as a differentiation marker. Redistributions in colonic neoplasia. Am J Pathol. 1989 Dec;135(6):1197–1212. [PMC free article] [PubMed] [Google Scholar]
- van Meer G., Simons K. The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells. EMBO J. 1986 Jul;5(7):1455–1464. doi: 10.1002/j.1460-2075.1986.tb04382.x. [DOI] [PMC free article] [PubMed] [Google Scholar]