Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation (original) (raw)
. 1998 Jan;152(1):135–144.
Abstract
The maintenance of adult tissue architecture is largely dependent on the function of cadherins. E-cadherin is expressed in most epithelia, although it may be co-expressed with P-cadherin in basal layers of stratified epithelia. Adhesive function of cadherins relies on interactions with catenins. Many reports have characterized reduced expression of cadherins and catenins in tumors, including those of the gastrointestinal tract. This study aimed to characterize expression of E- and P-cadherins, and the catenins, in the progression of Barrett's esophagus to adenocarcinoma. Immunohistochemical analysis and Western blotting were performed on paraffin-embedded and fresh-frozen tissue using antisera to the selected cadherins and catenins. The results of this study have shown inappropriate expression of cadherins and catenins in neoplastic Barrett's mucosa. There was a significant reduction of E-cadherin expression as the Barrett's metaplasia-dysplasia-adenocarcinoma sequence progressed (P < 0.01). In contrast, P-cadherin, expressed in basal layers of squamous esophagus, was usually absent from Barrett's and dysplasia but was expressed in 17 of 24 carcinomas, especially at the advancing tumor edge. Reduced expression of catenins was also seen, but in some specimens, immunoreactivity was observed in neoplastic nuclei, suggesting mediation of a nuclear function such as transcriptional regulation.
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Albelda S. M. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993 Jan;68(1):4–17. [PubMed] [Google Scholar]
- 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]
- Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
- Blot W. J. Esophageal cancer trends and risk factors. Semin Oncol. 1994 Aug;21(4):403–410. [PubMed] [Google Scholar]
- Bongiorno P. F., al-Kasspooles M., Lee S. W., Rachwal W. J., Moore J. H., Whyte R. I., Orringer M. B., Beer D. G. E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's oesophagus. Br J Cancer. 1995 Jan;71(1):166–172. doi: 10.1038/bjc.1995.34. [DOI] [PMC free article] [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., Giroldi L. A., van Bokhoven A., Schalken J. A. Transcriptional regulation of the human E-cadherin gene in human prostate cancer cell lines: characterization of the human E-cadherin gene promoter. Biochem Biophys Res Commun. 1994 Sep 15;203(2):1284–1290. doi: 10.1006/bbrc.1994.2321. [DOI] [PubMed] [Google Scholar]
- Candidus S., Bischoff P., Becker K. F., Höfler H. No evidence for mutations in the alpha- and beta-catenin genes in human gastric and breast carcinomas. Cancer Res. 1996 Jan 1;56(1):49–52. [PubMed] [Google Scholar]
- Dent J., Bremner C. G., Collen M. J., Haggitt R. C., Spechler S. J. Barrett's oesophagus. J Gastroenterol Hepatol. 1991 Jan-Feb;6(1):1–22. doi: 10.1111/j.1440-1746.1991.tb01137.x. [DOI] [PubMed] [Google Scholar]
- Dorudi S., Hanby A. M., Poulsom R., Northover J., Hart I. R. Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. Br J Cancer. 1995 Mar;71(3):614–616. doi: 10.1038/bjc.1995.119. [DOI] [PMC free article] [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]
- Gabbert H. E., Mueller W., Schneiders A., Meier S., Moll R., Birchmeier W., Hommel G. Prognostic value of E-cadherin expression in 413 gastric carcinomas. Int J Cancer. 1996 Jun 21;69(3):184–189. doi: 10.1002/(SICI)1097-0215(19960621)69:3<184::AID-IJC6>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
- Haggitt R. C. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994 Oct;25(10):982–993. doi: 10.1016/0046-8177(94)90057-4. [DOI] [PubMed] [Google Scholar]
- Hinck L., Näthke I. S., Papkoff J., Nelson W. J. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. doi: 10.1083/jcb.125.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoschuetzky H., Aberle H., Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994 Dec;127(5):1375–1380. doi: 10.1083/jcb.127.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hyafil F., Morello D., Babinet C., Jacob F. A cell surface glycoprotein involved in the compaction of embryonal carcinoma cells and cleavage stage embryos. Cell. 1980 Oct;21(3):927–934. doi: 10.1016/0092-8674(80)90456-0. [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., Babinet C., Eisen H., Jacob F. Surface antigen in early differentiation. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4449–4452. doi: 10.1073/pnas.74.10.4449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mareel M., Vleminckx K., Vermeulen S., Bracke M., Van Roy F. E-cadherin expression: a counterbalance for cancer cell invasion. Bull Cancer. 1992;79(4):347–355. [PubMed] [Google Scholar]
- McNeill H., Ozawa M., Kemler R., Nelson W. J. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell. 1990 Jul 27;62(2):309–316. doi: 10.1016/0092-8674(90)90368-o. [DOI] [PubMed] [Google Scholar]
- Molenaar M., van de Wetering M., Oosterwegel M., Peterson-Maduro J., Godsave S., Korinek V., Roose J., Destrée O., Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391–399. doi: 10.1016/s0092-8674(00)80112-9. [DOI] [PubMed] [Google Scholar]
- Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [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. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. doi: 10.1002/j.1460-2075.1988.tb03249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oyama T., Kanai Y., Ochiai A., Akimoto S., Oda T., Yanagihara K., Nagafuchi A., Tsukita S., Shibamoto S., Ito F. A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res. 1994 Dec 1;54(23):6282–6287. [PubMed] [Google Scholar]
- Ozawa M., Ringwald M., Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. doi: 10.1073/pnas.87.11.4246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palacios J., Benito N., Pizarro A., Suárez A., Espada J., Cano A., Gamallo C. Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. Am J Pathol. 1995 Mar;146(3):605–612. [PMC free article] [PubMed] [Google Scholar]
- Pignatelli M. E-cadherin: a biological marker of tumour differentiation. J Pathol. 1993 Oct;171(2):81–82. doi: 10.1002/path.1711710204. [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]
- Schipper J. H., Frixen U. H., Behrens J., Unger A., Jahnke K., Birchmeier W. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991 Dec 1;51(23 Pt 1):6328–6337. [PubMed] [Google Scholar]
- Shimazui T., Schalken J. A., Giroldi L. A., Jansen C. F., Akaza H., Koiso K., Debruyne F. M., Bringuier P. P. Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. Cancer Res. 1996 Sep 15;56(18):4154–4158. [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]
- Shiozaki H., Iihara K., Oka H., Kadowaki T., Matsui S., Gofuku J., Inoue M., Nagafuchi A., Tsukita S., Mori T. Immunohistochemical detection of alpha-catenin expression in human cancers. Am J Pathol. 1994 Apr;144(4):667–674. [PMC free article] [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]
- Swami S., Kumble S., Triadafilopoulos G. E-cadherin expression in gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma: an immunohistochemical and immunoblot study. Am J Gastroenterol. 1995 Oct;90(10):1808–1813. [PubMed] [Google Scholar]
- Takayama T., Shiozaki H., Shibamoto S., Oka H., Kimura Y., Tamura S., Inoue M., Monden T., Ito F., Monden M. Beta-catenin expression in human cancers. Am J Pathol. 1996 Jan;148(1):39–46. [PMC free article] [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. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988 Apr;102(4):639–655. doi: 10.1242/dev.102.4.639. [DOI] [PubMed] [Google Scholar]
- Tsukita S., Itoh M., Nagafuchi A., Yonemura S., Tsukita S. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J Cell Biol. 1993 Dec;123(5):1049–1053. doi: 10.1083/jcb.123.5.1049. [DOI] [PMC free article] [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]
- Yonemura Y., Ninomiya I., Kaji M., Sugiyama K., Fujimura T., Tsuchihara K., Kawamura T., Miyazaki I., Endou Y., Tanaka M. Decreased E-cadherin expression correlates with poor survival in patients with gastric cancer. Anal Cell Pathol. 1995 Mar;8(2):177–190. [PubMed] [Google Scholar]
- van der Burgh A., Dees J., Hop W. C., van Blankenstein M. Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus. Gut. 1996 Jul;39(1):5–8. doi: 10.1136/gut.39.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]