Scherbarth S, Orr F W
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Cancer Res. 1997 Sep 15;57(18):4105-10.
There have been few reported visual observations of metastatic cancer cell arrest in vivo. To seek evidence that inducible vascular adhesive properties can regulate hepatic metastasis, groups of 9-14 c57bl/6 mice were given 1.5 microg of interleukin-1alpha (IL-1alpha) 4 h before the injection of 3 x 10(5) B16F1 melanoma cells into a mesenteric vein. After 7 days, these mice had an 11-22-fold greater hepatic tumor burden than controls given i.p. saline. In both groups, small metastases were seen in the portal tract region. Twice as many 125I-labeled UdR-labeled B16F1 cells were detected in the livers of IL-1alpha-treated animals 5 min after injection, and 7 times as many were found after 24 h. Intravital videomicroscopy showed marked differences in the arrest pattern of the B16F1 cells between controls and IL-1alpha-treated mice. In controls, arrest occurred at a median distance of 32 microm beyond the sinusoidal inlet, where the median sinusoidal diameter was 16 microm. However, in IL-1alpha-treated mice, arrest occurred in the presinusoidal portal vein branches, which had a median diameter of 34 microm. Maximum observed tumor cell velocities were 2-fold less in the IL-1alpha-treated mice, although there was no significant difference in the flow rate of RBCs. To look for effects on the adhesive properties of the hepatic microvasculature, 5 x 10(4) B16F1 cells were incubated for 15 min on 5-microm sections of liver from control and IL-1alpha-treated mice. Three-fold more cells adhered to sections of liver from IL-1alpha-treated mice. This phenomenon was blocked by GRGDS peptides and by antibodies to E-selectin, ICAM-1, VCAM-1, and the alpha v integrin subunit. We postulate that pretreatment of mice with IL-1alpha alters a number of adhesive interactions between B16F1 cells and the hepatic microvasculature, contributing to the site of arrest and to the subsequent fate of the arrested cells.
体内转移性癌细胞停滞的可视化观察报道较少。为了寻找可诱导的血管黏附特性能够调节肝转移的证据，在将3×10⁵个B16F1黑色素瘤细胞注入肠系膜静脉前4小时，给9至14只C57BL/6小鼠每组注射1.5微克白细胞介素-1α（IL-1α）。7天后，这些小鼠的肝肿瘤负荷比腹腔注射生理盐水的对照组高11至22倍。在两组中，门静脉区域均可见小转移灶。注射后5分钟，在IL-1α处理动物的肝脏中检测到的¹²⁵I标记的尿苷标记的B16F1细胞是对照组的两倍，24小时后是对照组的7倍。活体视频显微镜显示，对照组和IL-1α处理小鼠之间B16F1细胞的停滞模式存在显著差异。在对照组中，停滞发生在窦状隙入口后方32微米的中位距离处，此处窦状隙的中位直径为16微米。然而，在IL-1α处理的小鼠中，停滞发生在窦前门静脉分支中，其直径中位值为34微米。在IL-1α处理的小鼠中观察到的肿瘤细胞最大速度降低了两倍，尽管红细胞流速没有显著差异。为了寻找对肝微血管黏附特性的影响，将5×10⁴个B16F1细胞在来自对照组和IL-1α处理小鼠的5微米肝切片上孵育15分钟。黏附到IL-1α处理小鼠肝脏切片上的细胞多三倍。这种现象被GRGDS肽以及抗E-选择素、ICAM-1、VCAM-1和αv整合素亚基的抗体所阻断。我们推测，用IL-1α对小鼠进行预处理会改变B16F1细胞与肝微血管之间的多种黏附相互作用，从而影响停滞部位以及停滞细胞的后续命运。
