Suwa T, Hinoda Y, Makiguchi Y, Takahashi T, Itoh F, Adachi M, Hareyama M, Imai K
First Department of Internal Medicine, Sapporo Medical University, Japan.
Int J Cancer. 1998 May 4;76(3):377-82. doi: 10.1002/(sici)1097-0215(19980504)76:3<377::aid-ijc15>3.0.co;2-8.
MUC1 mucin is an anti-adhesion molecule expressed in a wide variety of tumors. To examine whether MUC1 mucin is involved in tumor invasion, we have prepared MUC1 transfectants using the human gastric cancer cell line MKN74 and performed an in vivo tumor assay by transplanting these into nude mice. Tumor weight at 71 days after s.c. injection of transfectants was measured, showing that the in vivo growth of MUC1 transfectants was increased compared to that of mock transfectants. Furthermore, MUC1-transfectant tumors invaded into the muscle layer, whereas mock-transfectant tumors did not. In vitro invasion, adhesion to extracellular matrix components and phagokinetic track motility were then evaluated to analyze the mechanisms for the in vivo invasiveness of the transfectants. MUC1 transfectants exhibited an increased in vitro invasiveness, decreased binding to laminin, fibronectin, type I collogen and type IV collagen and increased motility. These effects of MUC1 mucin over-expression in MKN74 cells were abolished by the treatment of transfectants with an inhibitor of O-glycan biosynthesis, benzyl-alpha-GalNAc. Our data suggest that MUC1 mucin could be related to the increased invasive ability of MKN74 cells, whereas O-glycan might play an essential role.
MUC1黏蛋白是一种在多种肿瘤中表达的抗黏附分子。为了研究MUC1黏蛋白是否参与肿瘤侵袭，我们使用人胃癌细胞系MKN74制备了MUC1转染细胞，并将其移植到裸鼠体内进行体内肿瘤检测。测量皮下注射转染细胞71天后的肿瘤重量，结果显示与空载体转染细胞相比，MUC1转染细胞的体内生长有所增加。此外，MUC1转染细胞的肿瘤侵袭到了肌层，而空载体转染细胞的肿瘤则没有。随后评估了体外侵袭、与细胞外基质成分的黏附以及吞噬运动轨迹的运动能力，以分析转染细胞体内侵袭性的机制。MUC1转染细胞表现出体外侵袭性增加、与层粘连蛋白、纤连蛋白、I型胶原和IV型胶原的结合减少以及运动能力增强。用O-聚糖生物合成抑制剂苄基-α-GalNAc处理转染细胞后，MUC1黏蛋白在MKN74细胞中过表达的这些效应被消除。我们的数据表明，MUC1黏蛋白可能与MKN74细胞侵袭能力的增加有关，而O-聚糖可能起着至关重要的作用。
