Abstract
Reduced expression of E-cadherin, a Ca(2+)-dependent cell adhesion molecule present in normal epithelium, has been associated with invasive and metastatic cancer. Immunohistochemistry was used in examining the relationship between E-cadherin expression and stage in 59 oesophageal and 52 lung cancers. Advanced-stage oesophageal cancers were associated with both reduced and disorganised E-cadherin expression (P < 0.01). Advanced-stage lung adenocarcinomas generally exhibited disorganised or reduced E-cadherin expression, but no statistical association between expression pattern and stage was found (P > 0.05). No differences in stage were seen between tumours with reduced or disorganised E-cadherin expression. Altered E-cadherin expression was detected in dysplastic, non-invasive Barrett's oesophagus. Importantly, high-level E-cadherin expression was detected in 17 of 17 lymph nodes containing metastatic cancer. E-cadherin mRNA expression was decreased in tumours with reduced protein expression, but not in tumours with disorganised expression. Expression of alpha-catenin mRNA, an E-cadherin-associated protein, was detected in tissues with altered E-cadherin protein expression. Reduced and disorganised expression of E-cadherin appear to be related to transcriptional and post-translational events respectively, and both appear to represent altered cell adhesion associated with invasion and metastasis in thoracic neoplasms.
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- Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bowie G. L., Caslin A. W., Roland N. J., Field J. K., Jones A. S., Kinsella A. R. Expression of the cell-cell adhesion molecule E-cadherin in squamous cell carcinoma of the head and neck. Clin Otolaryngol Allied Sci. 1993 Jun;18(3):196–201. doi: 10.1111/j.1365-2273.1993.tb00829.x. [DOI] [PubMed] [Google Scholar]
- Brabant G., Hoang-Vu C., Cetin Y., Dralle H., Scheumann G., Mölne J., Hansson G., Jansson S., Ericson L. E., Nilsson M. E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res. 1993 Oct 15;53(20):4987–4993. [PubMed] [Google Scholar]
- Bringuier P. P., Umbas R., Schaafsma H. E., Karthaus H. F., Debruyne F. M., Schalken J. A. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 1993 Jul 15;53(14):3241–3245. [PubMed] [Google Scholar]
- Bussemakers M. J., van Bokhoven A., Mees S. G., Kemler R., Schalken J. A. Molecular cloning and characterization of the human E-cadherin cDNA. Mol Biol Rep. 1993 Feb;17(2):123–128. doi: 10.1007/BF00996219. [DOI] [PubMed] [Google Scholar]
- Dorudi S., Sheffield J. P., Poulsom R., Northover J. M., Hart I. R. E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study. Am J Pathol. 1993 Apr;142(4):981–986. [PMC free article] [PubMed] [Google Scholar]
- Eidelman S., Damsky C. H., Wheelock M. J., Damjanov I. Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors. Am J Pathol. 1989 Jul;135(1):101–110. [PMC free article] [PubMed] [Google Scholar]
- Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanson L. A., Nuzum E. O., Jones B. C., Malkinson A. M., Beer D. G. Expression of the glucocorticoid receptor and K-ras genes in urethan-induced mouse lung tumors and transformed cell lines. Exp Lung Res. 1991 Mar-Apr;17(2):371–387. doi: 10.3109/01902149109064425. [DOI] [PubMed] [Google Scholar]
- Hirano S., Kimoto N., Shimoyama Y., Hirohashi S., Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. doi: 10.1016/0092-8674(92)90103-j. [DOI] [PubMed] [Google Scholar]
- Kadowaki T., Shiozaki H., Inoue M., Tamura S., Oka H., Doki Y., Iihara K., Matsui S., Iwazawa T., Nagafuchi A. E-cadherin and alpha-catenin expression in human esophageal cancer. Cancer Res. 1994 Jan 1;54(1):291–296. [PubMed] [Google Scholar]
- Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993 Sep;9(9):317–321. doi: 10.1016/0168-9525(93)90250-l. [DOI] [PubMed] [Google Scholar]
- Lee S. W., Tomasetto C., Paul D., Keyomarsi K., Sager R. Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. J Cell Biol. 1992 Sep;118(5):1213–1221. doi: 10.1083/jcb.118.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mareel M. M., Behrens J., Birchmeier W., De Bruyne G. K., Vleminckx K., Hoogewijs A., Fiers W. C., Van Roy F. M. Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. Int J Cancer. 1991 Apr 1;47(6):922–928. doi: 10.1002/ijc.2910470623. [DOI] [PubMed] [Google Scholar]
- Matsuura K., Kawanishi J., Fujii S., Imamura M., Hirano S., Takeichi M., Niitsu Y. Altered expression of E-cadherin in gastric cancer tissues and carcinomatous fluid. Br J Cancer. 1992 Dec;66(6):1122–1130. doi: 10.1038/bjc.1992.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer B., Johnson J. P., Leitl F., Jauch K. W., Heiss M. M., Schildberg F. W., Birchmeier W., Funke I. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993 Apr 1;53(7):1690–1695. [PubMed] [Google Scholar]
- Morton R. A., Ewing C. M., Nagafuchi A., Tsukita S., Isaacs W. B. Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res. 1993 Aug 1;53(15):3585–3590. [PubMed] [Google Scholar]
- Nagafuchi A., Shirayoshi Y., Okazaki K., Yasuda K., Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987 Sep 24;329(6137):341–343. doi: 10.1038/329341a0. [DOI] [PubMed] [Google Scholar]
- Nagafuchi A., Takeichi M., Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. doi: 10.1016/0092-8674(91)90392-c. [DOI] [PubMed] [Google Scholar]
- Oda T., Kanai Y., Shimoyama Y., Nagafuchi A., Tsukita S., Hirohashi S. Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a human cancer cell line. Biochem Biophys Res Commun. 1993 Jun 30;193(3):897–904. doi: 10.1006/bbrc.1993.1710. [DOI] [PubMed] [Google Scholar]
- Oka H., Shiozaki H., Kobayashi K., Inoue M., Tahara H., Kobayashi T., Takatsuka Y., Matsuyoshi N., Hirano S., Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993 Apr 1;53(7):1696–1701. [PubMed] [Google Scholar]
- Piepenhagen P. A., Nelson W. J. Defining E-cadherin-associated protein complexes in epithelial cells: plakoglobin, beta- and gamma-catenin are distinct components. J Cell Sci. 1993 Mar;104(Pt 3):751–762. doi: 10.1242/jcs.104.3.751. [DOI] [PubMed] [Google Scholar]
- Roark E. F., Paradies N. E., Lagunowich L. A., Grunwald G. B. Evidence for endogenous proteases, mRNA level and insulin as multiple mechanisms of N-cadherin down-regulation during retinal development. Development. 1992 Apr;114(4):973–984. doi: 10.1242/dev.114.4.973. [DOI] [PubMed] [Google Scholar]
- Rubinfeld B., Souza B., Albert I., Müller O., Chamberlain S. H., Masiarz F. R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. doi: 10.1126/science.8259518. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
- Shimoyama Y., Nagafuchi A., Fujita S., Gotoh M., Takeichi M., Tsukita S., Hirohashi S. Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 1992 Oct 15;52(20):5770–5774. [PubMed] [Google Scholar]
- Su L. K., Vogelstein B., Kinzler K. W. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. doi: 10.1126/science.8259519. [DOI] [PubMed] [Google Scholar]
- Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
- Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993 Oct;5(5):806–811. doi: 10.1016/0955-0674(93)90029-p. [DOI] [PubMed] [Google Scholar]
- Takeichi M. Cadherins: a molecular family important in selective cell-cell adhesion. Annu Rev Biochem. 1990;59:237–252. doi: 10.1146/annurev.bi.59.070190.001321. [DOI] [PubMed] [Google Scholar]
- Umbas R., Schalken J. A., Aalders T. W., Carter B. S., Karthaus H. F., Schaafsma H. E., Debruyne F. M., Isaacs W. B. Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. Cancer Res. 1992 Sep 15;52(18):5104–5109. [PubMed] [Google Scholar]
- Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]