E-cadherin-dependent intercellular adhesion enhances chemoresistance

E-cadherin, an intercellular adhesion molecule, is important in cell growth and differentiation. Adhesion between cells is thought to decrease as cancers develop and disseminate. Knowledge of the effect of cell adhesion on proliferation and chemosensitivity may help individualize cancer treatment. Lovo and MCF-7 cells, which express E-cadherin, and PC-3 cells, which do not, were used in this study. Proliferation and chemosensitivity were measured in two-dimensional (2-D) culture and three-dimensional (3-D) culture. Protein and mRNA expression of E-cadherin, catenin, and cyclin-dependent kinase inhibitors were determined. Growth of Lovo and MCF-7 but not PC-3 cells was markedly suppressed in 3-D relative to 2-D. MCF-7 cells express high levels for E-cadherin, catenin, and p27 in 3-D, but catenin and p27 expression was decreased by exposure to anti-E-cadherin neutralizing antibody. Chemosensitivity of PC-3 was similar in 2-D and 3-D, but chemosensitivity of Lovo and MCF-7 was less in 3-D than 2-D. Moreover, the presence of anti-E-cadherin antibody increased chemosensitivity of MCF-7 in 3-D. E-cadherin affected the regulation of cell proliferation and differentiation, and decreased chemosensitivity. Chemosensitivity of cancer is affected by the state of cell adhesion and expression of intercellular adhesion molecules. Consideration of intercellular adherence characteristics in different chemosensitivity tests is likely to improve their reliability.