BACKGROUND.
Cadherins are the family of functionally related transmembrane glycoproteins responsible for the Ca"-dependent cellkell adhesion mechanism that is crucial for the mutual association of vertebrate cells. Because cell dissociation and acquisition of cell motility occur in cancer invasion and metastasis, it is important to study the possible involvement of mutual cell adhesion of cancer cells.
METHODS.
The results and observations reported in the literature on the involvement of cadherin-mediated adhesion in the behavior of cancer cells are reviewed and compared with the authors' experimental and clinical studies.
RESULTS.
In the initial studies, E-cadherin and cr-catenin o r 0-catenin expression have been investigated immunohistocheniically. Although these molecules showed strong expression in noncancerous epithelial tissues without exception, the reduction of the imrnunoreactivities of cancer cells has been observed. These observations suggest that the impaired E-cadherin mediated adhesion system is a characteristic of cells with malignant transformation. The impaired expression of 1: - cadherin is frequently observed in tumors with aggressive histopathologic characteristics that are defined by morphologic degree of invasiveness and metastasis.
Three mechanisms of the inactivation of cadherin action could be proposed in human cancers by in vivo and in vitro studies. The first is downregulation of Ecadherin expression and its gene mutation. The second is ahiiorniality or deletion of catenins, including the absence of tr-catenin. The third abnormality of this adhesion system is biochemical modification of catenins such as the phosphorylation of B-catenin.
CONCLUSIONS.
Numerous studies have suggested that the li-cadherin adhesion system is disturbed in cancer cells through various mechanisms and these impaired functions of E-cadherin contribute to the release of cancer cells from the primary lesion and to cell dedifferentiation.