Abnormalities of cell adhesion molecules in multistage carcinogenesis

Y. Kanai, Y. Shimoyama, T. Oda, S. Hirohashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Invasion and metastasis are later but critically important steps in multistage carcinogenesis. The inactivation of E (epithelial)-cadherin, which is a Ca2+-dependent cell-cell adhesion molecule, may trigger the release of cancer cells from the cancer nests. In fact, the invasion suppressing function of E-cadherin has been shown in in vitro studies. Furthermore, E-cadherin expression was strong in well differentiated carcinomas, whereas generally reduced in undifferentiated ones showing the strong invasive property. In spite of the above general rule, we found that a sizable proportion of undifferentiated gastric adenocarcinomas showing scattered histological growth pattern had definite E-cadherin expression. Therefore, human carcinoma cell lines lacking tight cell-cell adhesion were examined to clarify if alterations in catenins, which are cytoplasmic proteins interacting with cadherins, and/or structural abnormalities of normally expressed E-cadherin caused the dysfunction of the cell-cell adhesion system. Homologous deletion of part of the α-catenin gene with markedly reduced expression was observed in a human lung cancer cell line, PC9. mRNA sequence abnormalities of E-cadherin were detected in two human gastric cancer cell lines, MKN 45 and KATO-III. The wild-type allele of E-cadherin locus was lost in the two cell lines, indicating that E-cadherin gene was inactivated by a combination of loss of gene and mutation, similar to the mechanism which inactivated tumor suppressor genes. These findings suggested that varying genetic abnormalities of cell adhesion molecules could participate in multistage carcinogenesis, especially in the processes of invasion and metastasis.

Original languageEnglish
Pages (from-to)127-138
Number of pages12
JournalGann Monographs on Cancer Research
Volume42
Publication statusPublished - 1994 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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