McCarthy J B, Furcht L T
J Cell Biol. 1984 Apr;98(4):1474-80. doi: 10.1083/jcb.98.4.1474.
The migration of tumor cells through basement membranes and extracellular matrices is an integral component of tumor invasion and metastasis. Laminin and fibronectin are two basement membrane- and extracellular matrix-associated noncollagenous glycoproteins that have been shown to promote both cell adhesion and motility. Purified preparations of laminin and fibronectin stimulated the directed migration of B16 murine metastatic melanoma cells in vitro as assessed in modified Boyden chambers. The stimulation of migration occurred over a concentration range of 1-100 micrograms/ml of laminin or fibronectin, with a peak response occurring between 12.5 and 25 micrograms/ml. The maximal response of these cells was 80-120-fold higher than control migration. Affinity-purified antibody preparations specifically abrogated the migration of these cells in response to the respective proteins. Tumor cells in suspension were preincubated in physiologic levels of plasma fibronectin prior to assay to partially mimic what occurs when a metastasizing cell is in the blood stream. This preincubation with plasma fibronectin had no effect on the subsequent migration of cells in response to either laminin or fibronectin. Furthermore, experiments using filters precoated with fibronectin or laminin indicated that these cells could migrate by haptotaxis to these two proteins. We conclude that tumor cell migration in response to such noncollagenous adhesive glycoproteins could be an important aspect in the invasion and metastasis of certain malignant cell types.
肿瘤细胞穿过基底膜和细胞外基质的迁移是肿瘤侵袭和转移的一个重要组成部分。层粘连蛋白和纤连蛋白是两种与基底膜和细胞外基质相关的非胶原糖蛋白,已被证明可促进细胞黏附和运动。在改良的博伊登小室中评估发现,纯化的层粘连蛋白和纤连蛋白制剂可刺激B16小鼠转移性黑色素瘤细胞在体外的定向迁移。迁移刺激发生在层粘连蛋白或纤连蛋白浓度为1 - 100微克/毫升的范围内,峰值反应出现在12.5至25微克/毫升之间。这些细胞的最大反应比对照迁移高80 - 120倍。亲和纯化的抗体制剂可特异性消除这些细胞对相应蛋白质的迁移反应。在检测前,将悬浮的肿瘤细胞在生理水平的血浆纤连蛋白中预孵育,以部分模拟转移细胞在血流中的情况。这种与血浆纤连蛋白的预孵育对细胞随后对层粘连蛋白或纤连蛋白的迁移没有影响。此外,使用预涂有纤连蛋白或层粘连蛋白的滤膜进行的实验表明,这些细胞可以通过趋触性向这两种蛋白质迁移。我们得出结论,肿瘤细胞对这种非胶原黏附糖蛋白的迁移可能是某些恶性细胞类型侵袭和转移的一个重要方面。