Seiki M, Sato H, Liotta L A, Schiffmann E
Department of Virology, Kanazawa University, Ishikawa, Japan.
Int J Cancer. 1991 Nov 11;49(5):717-20. doi: 10.1002/ijc.2910490515.
Tumor-cell migration plays an essential role in invasion into surrounding tissues and the formation of metastatic colonies in distant organs. Metastatic human A2058 melanoma and ras-transfected NIH3T3 cells produce autocrine motility factors (AMFs) which stimulate their own motility, and the A2058 cell AMF (AMF/A2058) has been purified. In this study, we partially purified the AMF produced by N-ras-transfected NIH3T3 cells (AMF/NIH3T3) and compared it with AMF/A2058. The two AMFs differed in their gel filtration patterns and heat stability, although both elicited migration of N-ras-transfected NIH3T3 cells. The receptor for AMF/A2058 in A2058 cells is linked to a pertussis-toxin-sensitive GTP-binding protein. Pre-treatment of N-ras-transfected NIH3T3 cells with pertussis toxin also specifically blocked the promotion of motility by AMF/A2058, but did not affect the activity of AMF/NIH3T3. Stimulation of N-ras-transfected NIH3T3 cells by both AMFs elicited an additive response. Thus, the autocrine mechanisms of these two metastatic tumor cell lines are different with regard to the AMF molecules, receptors, and signal transduction pathways.
肿瘤细胞迁移在侵袭周围组织以及在远处器官形成转移瘤灶的过程中起着至关重要的作用。转移性人A2058黑色素瘤细胞和经ras转染的NIH3T3细胞可产生自分泌运动因子（AMF），这些因子能刺激细胞自身的运动，并且A2058细胞的AMF（AMF/A2058）已被纯化。在本研究中，我们对经N-ras转染的NIH3T3细胞产生的AMF（AMF/NIH3T3）进行了部分纯化，并将其与AMF/A2058进行比较。尽管两种AMF均可引发经N-ras转染的NIH3T3细胞的迁移，但它们在凝胶过滤图谱和热稳定性方面存在差异。A2058细胞中AMF/A2058的受体与一种对百日咳毒素敏感的GTP结合蛋白相关联。用百日咳毒素预处理经N-ras转染的NIH3T3细胞也可特异性地阻断AMF/A2058对细胞运动的促进作用，但不影响AMF/NIH3T3的活性。两种AMF对经N-ras转染的NIH3T3细胞的刺激引发了累加反应。因此，这两种转移性肿瘤细胞系的自分泌机制在AMF分子、受体和信号转导途径方面存在差异。
