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British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Oct;78(8):1095–1101. doi: 10.1038/bjc.1998.634

Characterization of soluble E-cadherin as a disease marker in gastric cancer patients.

J Gofuku 1, H Shiozaki 1, Y Doki 1, M Inoue 1, M Hirao 1, N Fukuchi 1, M Monden 1
PMCID: PMC2063146  PMID: 9792157

Abstract

The soluble fragment of E-cadherin protein (S-ECD) is reported to be increased in the peripheral blood of cancer patients. In this study, we investigated the clinical significance of serum S-ECD in 81 patients with gastric cancer. The amount of serum S-ECD was significantly higher in the gastric cancer patients (4735 +/- 2310 ng ml(-1)) than in healthy volunteers (2515 +/- 744 ng ml(-1)). With the normal range cut-off at average +2 s.d., 67% patients showed abnormally high serum S-ECD levels. This frequency was significantly higher than that of other tumour markers, such as CEA (4.4%) or CA19-9 (13.3%). However, there was no significant correlation between the amount of S-ECD and clinicopathological factors. Serum S-ECD might be derived from cancer tissue, as removal of cancers by surgical treatment results in quick decline of the serum S-ECD and S-ECD can be detected by immunoblot in cancer tissues but not in normal epithelium. The serum S-ECD amount was compared with the E-cadherin expression in cancer tissues, which were classified into those showing preserved (+), partially reduced (+/-) or lost (-) expression. Interestingly, E-cadherin (+/-) tumours showed higher serum S-ECD levels than the other types, and a higher amount of S-ECD in the immunoblot analysis. Thus, the serum level of S-ECD may serve as an excellent tumour marker with high sensitivity. Furthermore, analysis of S-ECD in serum and cancer tissue can offer clues for elucidating the mechanism of reduction of E-cadherin expression in cancer cells.

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Selected References

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  1. Nigam A. K., Savage F. J., Boulos P. B., Stamp G. W., Liu D., Pignatelli M. Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer. Br J Cancer. 1993 Sep;68(3):507–514. doi: 10.1038/bjc.1993.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Oka H., Shiozaki H., Kobayashi K., Tahara H., Tamura S., Miyata M., Doki Y., Iihara K., Matsuyoshi N., Hirano S. Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer. Virchows Arch A Pathol Anat Histopathol. 1992;421(2):149–156. doi: 10.1007/BF01607048. [DOI] [PubMed] [Google Scholar]
  3. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ozawa M., Engel J., Kemler R. Single amino acid substitutions in one Ca2+ binding site of uvomorulin abolish the adhesive function. Cell. 1990 Nov 30;63(5):1033–1038. doi: 10.1016/0092-8674(90)90506-a. [DOI] [PubMed] [Google Scholar]
  5. Peyriéras N., Hyafil F., Louvard D., Ploegh H. L., Jacob F. Uvomorulin: a nonintegral membrane protein of early mouse embryo. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6274–6277. doi: 10.1073/pnas.80.20.6274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Phillips M. L., Nudelman E., Gaeta F. C., Perez M., Singhal A. K., Hakomori S., Paulson J. C. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. doi: 10.1126/science.1701274. [DOI] [PubMed] [Google Scholar]
  7. Reinhardt K. M., Steiner M., Zillig D., Nagel H. R., Blann A. D., Brinckmann W. Soluble intercellular adhesion molecule-1 in colorectal cancer and its relationship to acute phase proteins. Neoplasma. 1996;43(2):65–67. [PubMed] [Google Scholar]
  8. Schadendorf D., Diehl S., Zuberbier T., Schadendorf C., Henz B. M. Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage. Dermatology. 1996;192(2):89–93. doi: 10.1159/000246328. [DOI] [PubMed] [Google Scholar]
  9. Shiozaki H., Oka H., Inoue M., Tamura S., Monden M. E-cadherin mediated adhesion system in cancer cells. Cancer. 1996 Apr 15;77(8 Suppl):1605–1613. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1605::AID-CNCR28>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  10. Shiozaki H., Tahara H., Oka H., Miyata M., Kobayashi K., Tamura S., Iihara K., Doki Y., Hirano S., Takeichi M. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Vessey C. J., Wilding J., Folarin N., Hirano S., Takeichi M., Soutter P., Stamp G. W., Pignatelli M. Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. J Pathol. 1995 Jun;176(2):151–159. doi: 10.1002/path.1711760208. [DOI] [PubMed] [Google Scholar]
  13. Yoshiura K., Kanai Y., Ochiai A., Shimoyama Y., Sugimura T., Hirohashi S. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7416–7419. doi: 10.1073/pnas.92.16.7416. [DOI] [PMC free article] [PubMed] [Google Scholar]

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