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. 1999 Nov;81(5):769–773. doi: 10.1038/sj.bjc.6690762

Detection of large molecular weight cytokeratin 8 as carrier protein of CA19–9 in non-small-cell lung cancer cell lines

J Fujita 1, N Dobashi 1, Y Ohtsuki 2, Y Ueda 1, S Bandoh 1, I Yamadori 3, J Takahara 1
PMCID: PMC2374310  PMID: 10555744

Abstract

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19–9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC. © 1999 Cancer Research Campaign

Keywords: antibody, CA19–9, cytokeratin 8, non-small-cell lung cancer

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Selected References

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  1. Basu A., Murthy U., Rodeck U., Herlyn M., Mattes L., Das M. Presence of tumor-associated antigens in epidermal growth factor receptors from different human carcinomas. Cancer Res. 1987 May 15;47(10):2531–2536. [PubMed] [Google Scholar]
  2. Blobel G. A., Moll R., Franke W. W., Vogt-Moykopf I. Cytokeratins in normal lung and lung carcinomas. I. Adenocarcinomas, squamous cell carcinomas and cultured cell lines. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(4):407–429. doi: 10.1007/BF02889883. [DOI] [PubMed] [Google Scholar]
  3. Broers J. L., Ramaekers F. C., Rot M. K., Oostendorp T., Huysmans A., van Muijen G. N., Wagenaar S. S., Vooijs G. P. Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies. Cancer Res. 1988 Jun 1;48(11):3221–3229. [PubMed] [Google Scholar]
  4. Burchill S. A., Bradbury M. F., Pittman K., Southgate J., Smith B., Selby P. Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction. Br J Cancer. 1995 Feb;71(2):278–281. doi: 10.1038/bjc.1995.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan R., Rossitto P. V., Edwards B. F., Cardiff R. D. Presence of proteolytically processed keratins in the culture medium of MCF-7 cells. Cancer Res. 1986 Dec;46(12 Pt 1):6353–6359. [PubMed] [Google Scholar]
  6. Chou C. F., Smith A. J., Omary M. B. Characterization and dynamics of O-linked glycosylation of human cytokeratin 8 and 18. J Biol Chem. 1992 Feb 25;267(6):3901–3906. [PubMed] [Google Scholar]
  7. Chu Y. W., Runyan R. B., Oshima R. G., Hendrix M. J. Expression of complete keratin filaments in mouse L cells augments cell migration and invasion. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4261–4265. doi: 10.1073/pnas.90.9.4261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donald P. J., Cardiff R. D., He D. E., Kendall K. Monoclonal antibody-porphyrin conjugate for head and neck cancer: the possible magic bullet. Otolaryngol Head Neck Surg. 1991 Dec;105(6):781–787. doi: 10.1177/019459989110500603. [DOI] [PubMed] [Google Scholar]
  9. Feizi T., Gooi H. C., Childs R. A., Picard J. K., Uemura K., Loomes L. M., Thorpe S. J., Hounsell E. F. Tumour-associated and differentiation antigens on the carbohydrate moieties of mucin-type glycoproteins. Biochem Soc Trans. 1984 Aug;12(4):591–596. doi: 10.1042/bst0120591. [DOI] [PubMed] [Google Scholar]
  10. Garrod D. R. Desmosomes and hemidesmosomes. Curr Opin Cell Biol. 1993 Feb;5(1):30–40. doi: 10.1016/s0955-0674(05)80005-5. [DOI] [PubMed] [Google Scholar]
  11. Godfroid E., Geuskens M., Dupressoir T., Parent I., Szpirer C. Cytokeratins are exposed on the outer surface of established human mammary carcinoma cells. J Cell Sci. 1991 Jul;99(Pt 3):595–607. doi: 10.1242/jcs.99.3.595. [DOI] [PubMed] [Google Scholar]
  12. Haga Y., Horiuchi S., Morino Y., Akagi M. Partial purification and characterization of CA19-9 antigen from the ascitic fluid of a patient with pancreatic cancer. Clin Biochem. 1989 Oct;22(5):363–368. doi: 10.1016/s0009-9120(89)80033-5. [DOI] [PubMed] [Google Scholar]
  13. Hanisch F. G., Uhlenbruck G., Dienst C., Stottrop M., Hippauf E. Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk. Eur J Biochem. 1985 Jun 3;149(2):323–330. doi: 10.1111/j.1432-1033.1985.tb08929.x. [DOI] [PubMed] [Google Scholar]
  14. Hanisch F. G., Uhlenbruck G., Dienst C. Structure of tumor-associated carbohydrate antigen Ca 19-9 on human seminal-plasma glycoproteins from healthy donors. Eur J Biochem. 1984 Nov 2;144(3):467–473. doi: 10.1111/j.1432-1033.1984.tb08489.x. [DOI] [PubMed] [Google Scholar]
  15. Hembrough T. A., Li L., Gonias S. L. Cell-surface cytokeratin 8 is the major plasminogen receptor on breast cancer cells and is required for the accelerated activation of cell-associated plasminogen by tissue-type plasminogen activator. J Biol Chem. 1996 Oct 11;271(41):25684–25691. doi: 10.1074/jbc.271.41.25684. [DOI] [PubMed] [Google Scholar]
  16. Hembrough T. A., Vasudevan J., Allietta M. M., Glass W. F., 2nd, Gonias S. L. A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines. J Cell Sci. 1995 Mar;108(Pt 3):1071–1082. doi: 10.1242/jcs.108.3.1071. [DOI] [PubMed] [Google Scholar]
  17. Hendrix M. J., Seftor E. A., Chu Y. W., Trevor K. T., Seftor R. E. Role of intermediate filaments in migration, invasion and metastasis. Cancer Metastasis Rev. 1996 Dec;15(4):507–525. doi: 10.1007/BF00054016. [DOI] [PubMed] [Google Scholar]
  18. Hintner H., Steinert P. M., Lawley T. J. Human upper epidermal cytoplasmic antibodies are directed against keratin intermediate filament proteins. J Clin Invest. 1983 Oct;72(4):1344–1351. doi: 10.1172/JCI111090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kalthoff H., Kreiker C., Schmiegel W. H., Greten H., Thiele H. G. Characterization of CA 19-9 bearing mucins as physiological exocrine pancreatic secretion products. Cancer Res. 1986 Jul;46(7):3605–3607. [PubMed] [Google Scholar]
  20. Klug T. L., LeDonne N. C., Greber T. F., Zurawski V. R., Jr Purification and composition of a novel gastrointestinal tumor-associated glycoprotein expressing sialylated lacto-N-fucopentaose II (CA 19-9). Cancer Res. 1988 Mar 15;48(6):1505–1511. [PubMed] [Google Scholar]
  21. Koprowski H., Steplewski Z., Mitchell K., Herlyn M., Herlyn D., Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979 Nov;5(6):957–971. doi: 10.1007/BF01542654. [DOI] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Magnani J. L., Steplewski Z., Koprowski H., Ginsburg V. Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res. 1983 Nov;43(11):5489–5492. [PubMed] [Google Scholar]
  24. Modjtahedi N., Frebourg T., Fossar N., Lavialle C., Cremisi C., Brison O. Increased expression of cytokeratin and ferritin-H genes in tumorigenic clones of the SW 613-S human colon carcinoma cell line. Exp Cell Res. 1992 Jul;201(1):74–82. doi: 10.1016/0014-4827(92)90349-d. [DOI] [PubMed] [Google Scholar]
  25. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  26. Mori M., Mimori K., Inoue H., Barnard G. F., Tsuji K., Nanbara S., Ueo H., Akiyoshi T. Detection of cancer micrometastases in lymph nodes by reverse transcriptase-polymerase chain reaction. Cancer Res. 1995 Aug 1;55(15):3417–3420. [PubMed] [Google Scholar]
  27. Ogawa J., Sano A., Koide S., Shohtsu A. Relation between recurrence and expression of proliferating cell nuclear antigen, sialyl LewisX, and sialyl Lewis(a) in lung cancer. J Thorac Cardiovasc Surg. 1994 Aug;108(2):329–336. [PubMed] [Google Scholar]
  28. Owaribe K., Nishizawa Y., Franke W. W. Isolation and characterization of hemidesmosomes from bovine corneal epithelial cells. Exp Cell Res. 1991 Feb;192(2):622–630. doi: 10.1016/0014-4827(91)90084-8. [DOI] [PubMed] [Google Scholar]
  29. Pendleton N., Occleston N. L., Walshaw M. J., Littler J. A., Jack C. I., Myskow M. W., Green J. A. Simple cytokeratins in the serum of patients with lung cancer: relationship to cell death. Eur J Cancer. 1994;30A(1):93–96. doi: 10.1016/s0959-8049(05)80026-7. [DOI] [PubMed] [Google Scholar]
  30. Schaafsma H. E., Ramaekers F. C., van Muijen G. N., Robben H., Lane E. B., Leigh I. M., Ooms E. C., Schalken J. A., van Moorselaar R. J., Ruiter D. J. Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases. Am J Pathol. 1991 Dec;139(6):1389–1400. [PMC free article] [PubMed] [Google Scholar]
  31. Schaafsma H. E., Van Der Velden L. A., Manni J. J., Peters H., Link M., Rutter D. J., Ramaekers F. C. Increased expression of cytokeratins 8, 18 and vimentin in the invasion front of mucosal squamous cell carcinoma. J Pathol. 1993 May;170(1):77–86. doi: 10.1002/path.1711700113. [DOI] [PubMed] [Google Scholar]
  32. Sugiyama K., Kawai T., Nagata N., Suzuki M. Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases. Hum Pathol. 1992 Aug;23(8):900–904. doi: 10.1016/0046-8177(92)90402-o. [DOI] [PubMed] [Google Scholar]
  33. Sundström B., Stigbrand T. A two-site enzyme-linked immunosorbent assay for cytokeratin 8. Int J Cancer. 1990 Oct 15;46(4):604–607. doi: 10.1002/ijc.2910460409. [DOI] [PubMed] [Google Scholar]
  34. Takada A., Ohmori K., Takahashi N., Tsuyuoka K., Yago A., Zenita K., Hasegawa A., Kannagi R. Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun. 1991 Sep 16;179(2):713–719. doi: 10.1016/0006-291x(91)91875-d. [DOI] [PubMed] [Google Scholar]
  35. Takada A., Ohmori K., Yoneda T., Tsuyuoka K., Hasegawa A., Kiso M., Kannagi R. Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res. 1993 Jan 15;53(2):354–361. [PubMed] [Google Scholar]
  36. 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. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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