Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jan;80(2):543–547. doi: 10.1073/pnas.80.2.543

Immunocytochemical identification of epithelium-derived human tumors with antibodies to desmosomal plaque proteins.

W W Franke, R Moll, H Mueller, E Schmid, C Kuhn, R Krepler, U Artlieb, H Denk
PMCID: PMC393415  PMID: 6340102

Abstract

Epithelial cells contain desmosomes, special intercellular junctions providing sites of membrane attachment for intermediate-sized filaments of the cytokeratin type (tonofilaments). Such sites of anchorage of tonofilaments appear as dense plaques on the cytoplasmic side of the desmosomal membrane. We have isolated desmosome-enriched fractions from bovine snout epidermis and tongue mucosa and have characterized the major protein associated with the desmosomal plaque. This protein occurs in equimolar amounts of two polypeptides of Mr 250,000 (desmoplakin I) and Mr 215,000 (desmoplakin II) which are chemically and immunologically related. Antibodies raised against desmoplakins allow the identification and localization of this protein in epithelial cells grown in tissues or in vitro and show crossreaction in species as diverse as man, mouse, and chicken. Using immunolocalization at the light and electron microscope levels, we show that these antibodies bind specifically to desmosomal plaques. Antibodies to desmoplakins have been used successfully for detection of desmosomal proteins in a broad variety of epithelium-derived human tumors, including primary carcinomas and their metastases, irrespective of the morphology of the specific tumor. Nonepithelial tumors examined have been negative. We propose to use antibodies to desmoplakins and to cytokeratins in pathological diagnosis as two independent markers for the positive immunocytochemical identification and classification of epithelium derived tumors.

Full text

PDF
543

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alroy J., Pauli B. U., Weinstein R. S. Correlation between numbers of desmosomes and the aggressiveness of transitional cell carcinoma in human urinary bladder. Cancer. 1981 Jan 1;47(1):104–112. doi: 10.1002/1097-0142(19810101)47:1<104::aid-cncr2820470118>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  2. Altmannsberger M., Osborn M., Hölscher A., Schauer A., Weber K. The distribution of keratin type intermediate filaments in human breast cancer. An immunohistological study. Virchows Arch B Cell Pathol Incl Mol Pathol. 1981;37(3):277–284. doi: 10.1007/BF02892576. [DOI] [PubMed] [Google Scholar]
  3. Asch B. B., Burstein N. A., Vidrich A., Sun T. T. Identification of mouse mammary epithelial cells by immunofluorescence with rabbit and guinea pig antikeratin antisera. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5643–5647. doi: 10.1073/pnas.78.9.5643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bannasch P., Zerban H., Schmid E., Franke W. W. Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4948–4952. doi: 10.1073/pnas.77.8.4948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Battifora H., Sun T. T., Bahu R. M., Rao S. The use of antikeratin antiserum as a diagnostic tool: thymoma versus lymphoma. Hum Pathol. 1980 Nov;11(6):635–641. doi: 10.1016/s0046-8177(80)80074-8. [DOI] [PubMed] [Google Scholar]
  6. Denk H., Krepler R., Lackinger E., Artlieb U., Franke W. W. Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice. Lab Invest. 1982 Jun;46(6):584–596. [PubMed] [Google Scholar]
  7. Drochmans P., Freudenstein C., Wanson J. C., Laurent L., Keenan T. W., Stadler J., Leloup R., Franke W. W. Structure and biochemical composition of desmosomes and tonofilaments isolated from calf muzzle epidermis. J Cell Biol. 1978 Nov;79(2 Pt 1):427–443. doi: 10.1083/jcb.79.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Franke W. W., Appelhans B., Schmid E., Freudenstein C., Osborn M., Weber K. Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin. Differentiation. 1979;15(1):7–25. doi: 10.1111/j.1432-0436.1979.tb01030.x. [DOI] [PubMed] [Google Scholar]
  10. Franke W. W., Denk H., Kalt R., Schmid E. Biochemical and immunological identification of cytokeratin proteins present in hepatocytes of mammalian liver tissue. Exp Cell Res. 1981 Feb;131(2):299–318. doi: 10.1016/0014-4827(81)90234-2. [DOI] [PubMed] [Google Scholar]
  11. Franke W. W., Schiller D. L., Moll R., Winter S., Schmid E., Engelbrecht I., Denk H., Krepler R., Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. doi: 10.1016/0022-2836(81)90460-5. [DOI] [PubMed] [Google Scholar]
  12. Franke W. W., Schmid E., Freudenstein C., Appelhans B., Osborn M., Weber K., Keenan T. W. Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol. 1980 Mar;84(3):633–654. doi: 10.1083/jcb.84.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Franke W. W., Schmid E., Grund C., Müller H., Engelbrecht I., Moll R., Stadler J., Jarasch E. D. Antibodies to high molecular weight polypeptides of desmosomes: specific localization of a class of junctional proteins in cells and tissue. Differentiation. 1981;20(3):217–241. doi: 10.1111/j.1432-0436.1981.tb01178.x. [DOI] [PubMed] [Google Scholar]
  14. Franke W. W., Schmid E., Osborn M., Weber K. Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5034–5038. doi: 10.1073/pnas.75.10.5034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Franke W. W., Schmid E., Weber K., Osborn M. HeLa cells contain intermediate-sized filaments of the prekeratin type. Exp Cell Res. 1979 Jan;118(1):95–109. doi: 10.1016/0014-4827(79)90587-1. [DOI] [PubMed] [Google Scholar]
  16. Franke W. W., Schmid E., Winter S., Osborn M., Weber K. Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res. 1979 Oct 1;123(1):25–46. doi: 10.1016/0014-4827(79)90418-x. [DOI] [PubMed] [Google Scholar]
  17. Franke W. W., Weber K., Osborn M., Schmid E., Freudenstein C. Antibody to prekeratin. Decoration of tonofilament like arrays in various cells of epithelial character. Exp Cell Res. 1978 Oct 15;116(2):429–445. doi: 10.1016/0014-4827(78)90466-4. [DOI] [PubMed] [Google Scholar]
  18. Fuchs E., Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. doi: 10.1016/0092-8674(80)90094-x. [DOI] [PubMed] [Google Scholar]
  19. Gabbiani G., Kapanci Y., Barazzone P., Franke W. W. Immunochemical identification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologist. Am J Pathol. 1981 Sep;104(3):206–216. [PMC free article] [PubMed] [Google Scholar]
  20. Kartenbeck J., Schmid E., Franke W. W., Geiger B. Different modes of internalization of proteins associated with adhaerens junctions and desmosomes: experimental separation of lateral contacts induces endocytosis of desmosomal plaque material. EMBO J. 1982;1(6):725–732. doi: 10.1002/j.1460-2075.1982.tb01237.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Krepler R., Denk H., Weirich E., Schmid E., Franke W. W. Keratin-like proteins in normal and neoplastic cells of human and rat mammary gland as revealed by immunofluorescence microscopy. Differentiation. 1981;20(3):242–252. doi: 10.1111/j.1432-0436.1981.tb01179.x. [DOI] [PubMed] [Google Scholar]
  22. Krohne G., Stick R., Kleinschmidt J. A., Moll R., Franke W. W., Hausen P. Immunological localization of a major karyoskeletal protein in nucleoli of oocytes and somatic cells of Xenopus laevis. J Cell Biol. 1982 Sep;94(3):749–754. doi: 10.1083/jcb.94.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lazarides E. Intermediate filaments as mechanical integrators of cellular space. Nature. 1980 Jan 17;283(5744):249–256. doi: 10.1038/283249a0. [DOI] [PubMed] [Google Scholar]
  24. Osborn M., Geisler N., Shaw G., Sharp G., Weber K. Intermediate filaments. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 1):413–429. doi: 10.1101/sqb.1982.046.01.040. [DOI] [PubMed] [Google Scholar]
  25. Pauli B. U., Cohen S. M., Alroy J., Weinstein R. S. Desmosome ultrastructure and biological behavior of chemical carcinogen-induced urinary bladder carcinomas. Cancer Res. 1978 Oct;38(10):3276–3285. [PubMed] [Google Scholar]
  26. Ramaekers F. C., Osborn M., Schimid E., Weber K., Bloemendal H., Franke W. W. Identification of the cytoskeletal proteins in lens-forming cells, a special epitheloid cell type. Exp Cell Res. 1980 Jun;127(2):309–327. doi: 10.1016/0014-4827(80)90437-1. [DOI] [PubMed] [Google Scholar]
  27. Schlegel R., Banks-Schlegel S., McLeod J. A., Pinkus G. S. Immunoperoxidase localization of keratin in human neoplasms: a preliminary survey. Am J Pathol. 1980 Oct;101(1):41–49. [PMC free article] [PubMed] [Google Scholar]
  28. Skerrow C. J., Matoltsy A. G. Isolation of epidermal desmosomes. J Cell Biol. 1974 Nov;63(2 Pt 1):515–523. doi: 10.1083/jcb.63.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sun T. T., Green H. Immunofluorescent staining of keratin fibers in cultured cells. Cell. 1978 Jul;14(3):469–476. doi: 10.1016/0092-8674(78)90233-7. [DOI] [PubMed] [Google Scholar]
  30. Sun T. T., Shih C., Green H. Keratin cytoskeletons in epithelial cells of internal organs. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2813–2817. doi: 10.1073/pnas.76.6.2813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wu Y. J., Rheinwald J. G. A new small (40 kd) keratin filament protein made by some cultured human squamous cell carcinomas. Cell. 1981 Sep;25(3):627–635. doi: 10.1016/0092-8674(81)90170-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES