Nakamura Tomoaki, Kato Yasushi, Fuji Hidenori, Horiuchi Tetsuya, Chiba Yukio, Tanaka Kuniyoshi
Second Department of Surgery, Fukui Medical University, Matsuoka-Cho, Yoshida-Gun, Fukui 910-1193, Japan.
Int J Mol Med. 2003 Nov;12(5):693-700.
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.
E-钙黏蛋白是一种细胞间黏附分子，在细胞生长和分化中起重要作用。随着癌症的发生和扩散，细胞间的黏附作用被认为会减弱。了解细胞黏附对增殖和化疗敏感性的影响可能有助于实现癌症治疗的个体化。本研究使用了表达E-钙黏蛋白的Lovo细胞和MCF-7细胞，以及不表达该蛋白的PC-3细胞。在二维（2-D）培养和三维（3-D）培养中测量细胞增殖和化疗敏感性。测定了E-钙黏蛋白、连环蛋白和细胞周期蛋白依赖性激酶抑制剂的蛋白质和mRNA表达。与二维培养相比，三维培养中Lovo细胞和MCF-7细胞（而非PC-3细胞）的生长明显受到抑制。MCF-7细胞在三维培养中E-钙黏蛋白、连环蛋白和p27表达水平较高，但暴露于抗E-钙黏蛋白中和抗体后，连环蛋白和p27表达降低。PC-3细胞在二维和三维培养中的化疗敏感性相似，但Lovo细胞和MCF-7细胞在三维培养中的化疗敏感性低于二维培养。此外，抗E-钙黏蛋白抗体的存在增加了MCF-7细胞在三维培养中的化疗敏感性。E-钙黏蛋白影响细胞增殖和分化的调节，并降低化疗敏感性。癌症的化疗敏感性受细胞黏附状态和细胞间黏附分子表达的影响。在不同的化疗敏感性测试中考虑细胞间黏附特性可能会提高其可靠性。
