Sakurai T, Yamada M, Simamura S, Motoyoshi K
Biochemical Reseach Laboratory, Morinaga Milk Industry Co. Ltd., Kanagawa pref., Japan.
Cancer Immunol Immunother. 1997 Mar;44(1):48-54. doi: 10.1007/s002620050354.
We studied the effect of recombinant human macrophage-colony-stimulating factor (rhM-CSF) on the formation of lung and liver metastases following the i.v. injection of the B16 melanoma subline (B16 LiLu) into mice. When rhM-CSF was administered before the B16 inoculation, the number of tumor metastases decreased in the lung and liver. However, the administration of rhM-CSF after B16 inoculation did not produce an antimetastatic effect in the lung, but did in the liver, B16 cells labeled with 5-[125I]-iodo-2'-deoxyuridine (125I-dUrd) were injected and the arrest of tumor cell emboli was examined in the capillary beds of the lung and liver of mice treated with either vehicle or rhM-CSF. In both groups, there were the same numbers of B16 cells in both the lung and the liver 3 minutes after the B16 injection, and almost all tumor cells died within 24 h. However, the number of cells surviving in the lung was decreased in mice injected with rhM-CSF (37%). There was no difference in the number of cells in the livers of mice treated either with vehicle or rhM-CSF in the first 24 h after tumor cell injection. The administration of rhM-CSF increased NK 1.1+ cells in the mouse spleen and facilitated NK activity in vivo. At the same time, the administration of an anti-NK 1.1 antibody blocked the antimetastatic effect of rhM-CSF in the lung but not in the liver. The antibody was effective only when it was injected before the B16 inoculation. These results suggest that the antimetastatic effect of rhM-CSF in the lung was mediated by NK 1.1+ cells within 24 h of B16 injection. In contrast, the antimetastatic effect of rhM-CSF in the liver was mediated not only by NK 1.1+ cells but also by other antimetastatic systems such as macrophages.
我们研究了重组人巨噬细胞集落刺激因子（rhM-CSF）对小鼠静脉注射B16黑色素瘤亚系（B16 LiLu）后肺和肝转移形成的影响。在接种B16之前给予rhM-CSF时，肺和肝中的肿瘤转移数量减少。然而，在接种B16后给予rhM-CSF对肺没有产生抗转移作用，但对肝有抗转移作用。注射用5-[125I]-碘-2'-脱氧尿苷（125I-dUrd）标记的B16细胞，并在接受赋形剂或rhM-CSF治疗的小鼠的肺和肝毛细血管床中检查肿瘤细胞栓子的滞留情况。在两组中，B16注射后3分钟，肺和肝中的B16细胞数量相同，并且几乎所有肿瘤细胞在24小时内死亡。然而，注射rhM-CSF的小鼠肺中存活的细胞数量减少（37%）。在肿瘤细胞注射后的最初24小时内，接受赋形剂或rhM-CSF治疗的小鼠肝脏中的细胞数量没有差异。给予rhM-CSF可增加小鼠脾脏中的NK 1.1+细胞，并促进体内NK活性。同时，给予抗NK 1.1抗体可阻断rhM-CSF在肺中的抗转移作用，但不能阻断在肝中的抗转移作用。该抗体仅在接种B16之前注射时有效。这些结果表明，rhM-CSF在肺中的抗转移作用在B16注射后24小时内由NK 1.1+细胞介导。相比之下，rhM-CSF在肝中的抗转移作用不仅由NK 1.1+细胞介导，还由其他抗转移系统如巨噬细胞介导。
