Summary
Conclusion
Our results indicate that loss of E-cadherin might be associated with a more invasive phenotype in pancreatic cancer.
Background
A reduced expression of the calcium-dependent E-cadherin cell-cell adhesion molecule on tumor cells has been described as an important factor for tumor invasion and metastasis.
Methods
Pancreatic tissues (carcinoma, chronic pancreatitis, and normal) as well as 12 pancreatic tumor cell lines were investigated for E-cadherin expression by immunohistochemistry. To correlate the motility of pancreatic tumor cells in vitro with E-cadherin expression, we used a Boyden chamber assay.
Results
In pancreatic carcinoma tissues, diffuse growing tumor cells showed a decrease or loss of E-cadherin expression, whereas in areas of compact tumor growth, only a slight decrease of E-cadherin expression was observed compared to normal pancreas or chronic pancreatitis. No correlation between the E-cadherin expression and the grading of the tumor cells, the tumor stage, or the disease progression was detectable. Of four tumor cell lines that migrated in the Boyden chamber, three were predominantly E-cadherin negative. In contrast, seven of eight cell lines that did not migrate in vitro revealed E-cadherin expression.
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References
Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator.Science (Washington) 1991; 251: 1451–1455.
Damsky CH, Richa J, Solter D, Knudsen K, Buck CA. Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue.Cell 1983; 34: 455–466.
Nagafuchi A, Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmatic domain.EMBO 1988; 7: 3679–3684.
Gumbiner B, Simons K. A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide.J Cell Biol 1986; 102: 457–468.
Nicolson GL. Cancer metastasis, tumor cell and host organ properties important in metastasis to specific secondary sites.Biochem Biophys Acta 1988; 948: 175–224.
Shiozaki H, Tahara H, Oka H. Expression of immunoreactive E-cadherin adhesion molecules in human cancers.Am J Pathol 1991; 139: 17–23.
Schipper JH, Frixen UH, 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; 51: 6328–6337.
Mayer B, Johnson JP, Leitl F. E-cadherin, expression in primary and metastatic gastric cancer: Downregulation correlates with cellular dedifferentiation and glandular disintegration.Cancer Res 1993; 53: 1690–1695.
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; 66: 107–119.
Frixen UH, Behrens J, Sachs M. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.J Cell Biol 1991; 113: 173–185.
Shimoyama Y, Hirohashi S, Hirano S. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas.Cancer Res 1989; 49: 2128–2133.
Bülow M, Schärfe T, Klöppel G, Kern HF. Establishment and characterisation of continuous tumor cell lines from human pancreatic carcinoma in vitro.Digestion 1982; 25: 17,18.
Elsässer HP, Lehr U, Agricola B, Kern HF. Structural analysis of a new highly metastatic cell line PaTu-8902 from a primary human pancreatic adenocarcinoma.Virchows Arch B 1993; 64: 201–207.
Elsässer HP, Lehr U, Agricola B, Kern HF. Establishment and characterisation of two cell lines with different grades of differentiation derived from one primary human pancreatic adenocarcinoma.Virchows Arch B 1992; 61: 295–306.
Tan MH, Nowak NJ, Loor R. Characterization of a new primary human pancreatic tumor line.Cancer Invest 1986; 4: 15–23.
Tan MH, Chu TM. Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC1) implanted orthotopically into nude mice.Tumor Biol 1986; 6: 89–98.
Lieber M, Mazzetta J, Nelson-Rees W, Kaplan M, Todaro G. Establishment of a continuous tumor-cell line (Panc-1) from a human carcinoma of the exocrine pancreas.Int J Cancer 1975; 15: 741–747.
Cordell JL, Falini B, Erber WN. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP Complexes).J Histochem Cytochem 1984; 12: 219–229.
Albini A, Iwamoto Y, Kleinman HK. A rapid in vitro assay for quantitating the invasive potential of tumor cells.Cancer Res 1987; 47: 3239–3245.
Böhm M, Totzeck B, Birchmeier W, Wieland I. Differences of E-cadherin expression levels and pattern in primary and metastatic human lung cancer.Clin Exp Metastasis 1994; 12: 55–62.
Miyata M, Shiozaki H, Iihara K. Relationship between E-cadherin expression and lymph node metastasis in human esophageal cancer.Int J Oncol 1994; 4: 61–65.
Eidelman S, Damsky CH, Wheelock MJ, Damjanov I. Expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in normal human tissues and tumors.Am J Pathol 1989; 135: 101–110.
Dorudi S, Sheffield JP, Poulsom R, Northover JMA, Hart IR. E-cadherin expression in colorectal cancer-an immuno-cytochemical and in situ hybridisation study.Am J Pathol 1993; 142: 981–986.
Nigam AK, Savage FJ, Boulos PB, Stamp GWH, Liu D, Pignatelli M. Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer.Br J Cancer 1993; 68: 507–514.
Pignatelli M, Ansari TW, Gunter P, Liu D, Hirano S, Takeichi M, Klöppel G, Lemoine NR. Loss of membranous E-cadherin expression in pancreatic cancer: correlation with lymph node metastasis, high grade, and advanced state.J Pathol 1994; 174: 243–248.
Becker KF, Atkinson MJ, Reich U. Exon skipping in the E-cadherin gene transcript in metastatic human gastric carcinomas.Hum Mol Genet 1993; 2: 803–804.
Hirano S, Kimoto N, Shimoyama Y, Hirohashi, S, Takeichi M. Identification of a neural a-catenin as a key regulator of cadherin function and multicellular organisation.Cancer Res 1992; 70: 293–301.
Chen W, Obrink B. Cell-cell contacts mediated by E-cadherin (Uvomorulin) restrict invasive behavior of L-cells.J Cell Biol 1991; 114: 319–327.
Sommers CL, Thompson EW, Torri JA, Kemler, R, Gelmann EP, Byers SW. Cell adhesio molecule uvomorulin expression in human breast cancer cell lines: relationship to morphology and invasive capacities.Cell Growth & Diff 1991; 2: 365–372.
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Weinel, R.J., Neumann, K., Kisker, O. et al. Expression and potential role of E-cadherin in pancreatic carcinoma. Int J Pancreatol 19, 25–30 (1996). https://doi.org/10.1007/BF02788372
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DOI: https://doi.org/10.1007/BF02788372