E Breen1, G Steele, A M Mercurio. 1. Laboratory of Cancer Biology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
BACKGROUND: The clinical behavior of colorectal cancer depends on its ability to invade and metastasize. Metastatic cells must dissociate from other cells and invade through basement membrane and stroma. Cell-cell adhesion in epithelial cells is mediated by the cell surface protein E-cadherin in association with alpha- and beta-catenin, which link E-cadherin to the cytoskeleton. Decreased cell-cell adhesion and increased motility on laminin have been correlated with more poorly differentiated and aggressive carcinomas. METHODS: In this study, the RKO cell line, previously shown by us to lack E-cadherin expression, was transfected with the complementary DNA for E-cadherin. The transfectants were selected for high levels of surface expression by sequential FACS and examined in functional assays. RESULTS: In comparison to control transfectants, the E-cadherin transfectants exhibited a more epithelial-like morphology, a 30% increase in Ca(2+)-dependent cell-cell aggregation, and a markedly reduced motility on the matrix proteins, collagen I and laminin. CONCLUSIONS: These data demonstrate that correction of a defect in the cadherin/catenin cell-cell adhesion complex, often found in poorly differentiated and highly invasive tumors, facilitates increased cell-cell adhesion and retards tumor cell migration on basement membrane and stromal proteins.
BACKGROUND: The clinical behavior of colorectal cancer depends on its ability to invade and metastasize. Metastatic cells must dissociate from other cells and invade through basement membrane and stroma. Cell-cell adhesion in epithelial cells is mediated by the cell surface protein E-cadherin in association with alpha- and beta-catenin, which link E-cadherin to the cytoskeleton. Decreased cell-cell adhesion and increased motility on laminin have been correlated with more poorly differentiated and aggressive carcinomas. METHODS: In this study, the RKO cell line, previously shown by us to lack E-cadherin expression, was transfected with the complementary DNA for E-cadherin. The transfectants were selected for high levels of surface expression by sequential FACS and examined in functional assays. RESULTS: In comparison to control transfectants, the E-cadherin transfectants exhibited a more epithelial-like morphology, a 30% increase in Ca(2+)-dependent cell-cell aggregation, and a markedly reduced motility on the matrix proteins, collagen I and laminin. CONCLUSIONS: These data demonstrate that correction of a defect in the cadherin/catenin cell-cell adhesion complex, often found in poorly differentiated and highly invasive tumors, facilitates increased cell-cell adhesion and retards tumor cell migration on basement membrane and stromal proteins.
Authors: K Herrenknecht; M Ozawa; C Eckerskorn; F Lottspeich; M Lenter; R Kemler Journal: Proc Natl Acad Sci U S A Date: 1991-10-15 Impact factor: 11.205
Authors: Adam Elzagheid; Abdelbaset Buhmeida; Eija Korkeila; Yrjö Collan; Kari Syrjänen; Seppo Pyrhönen Journal: World J Gastroenterol Date: 2008-08-21 Impact factor: 5.742