Weiss L, Ward P M, Holmes J C
Int J Cancer. 1983 Jul 15;32(1):79-83. doi: 10.1002/ijc.2910320113.
Following the injection of B16 melanoma cells into the portal veins of mice, all animals developed liver tumors, but only 16% developed lung tumors. Portal vein injections of radiolabelled B16 and Walker 256 cancer cells into mice and rats, respectively, revealed that all of the cells were temporarily arrested in the liver and most were then slowly released. Bioassays indicated that of 8 X 10(4) B16 cells released from the liver over 24 h after portal vein injections of 10(5) cells, only approximately 1% were delivered to the lungs in a viable state. Experiments made with radiolabelled B16 cells showed that transit through either the liver or lungs following portal vein or tail vein injections, respectively, resulted in massive death of cancer cells. It is suggested that the death of most circulating cancer cells passing through the first organ encountered after leaving their primary tumor, serves to severely limit their further direct spread to other organs. It is therefore expected that metastases to these other organs would, to a large extent, be generated by cancer cells from metastases in the "first organs" as distinct from direct seeding from cancer cells released from the primary tumor. If the results of the present experiments have general application, they serve to emphasize the importance of metastasis of metastases in the natural history of the spread of cancer. In a previous publication (Weiss, 1980), studies of lung-to-liver traffic of cancer cells in rats revealed that, after tail vein injections, most Walker 256 cells were temporarily arrested in the pulmonary vasculature and then slowly released. A large proportion of the released cancer cells were dead or lethally injured on release from the lungs, and this "first organ processing" apparently accounted for the comparative rarity of extrapulmonary tumors following tail vein injections. In this communication, the concept of "first organ processing" of circulating cancer cells is further examined with respect to the liver-to-lung traffic of B16 melanoma and Walker 256 cells injected into the portal veins of mice or rats respectively. Both of these cell types grow well in the lungs following tail-vein injection.
将B16黑色素瘤细胞注入小鼠门静脉后，所有动物均发生肝肿瘤，但只有16%发生肺肿瘤。分别将放射性标记的B16和Walker 256癌细胞注入小鼠和大鼠的门静脉后发现，所有细胞均暂时停滞在肝脏中，随后大多数细胞缓慢释放。生物测定表明，在门静脉注射10⁵个细胞后24小时内从肝脏释放的8×10⁴个B16细胞中，只有约1%以存活状态到达肺部。用放射性标记的B16细胞进行的实验表明，分别经门静脉或尾静脉注射后，癌细胞在肝脏或肺中转运时会大量死亡。有人提出，大多数离开原发肿瘤后遇到的第一个器官的循环癌细胞死亡，会严重限制它们进一步直接扩散到其他器官。因此，可以预期，转移到这些其他器官的转移瘤在很大程度上是由“第一个器官”中的转移瘤产生的癌细胞形成的，而不是由原发肿瘤释放的癌细胞直接播种形成的。如果本实验结果具有普遍适用性，那么它们就强调了转移瘤转移在癌症扩散自然史中的重要性。在之前的一篇出版物（Weiss，1980）中，对大鼠癌细胞从肺到肝的转运研究表明，尾静脉注射后，大多数Walker 256细胞暂时停滞在肺血管系统中，然后缓慢释放。从肺中释放的癌细胞中很大一部分在释放时已经死亡或受到致命损伤，这种“第一个器官处理”显然是尾静脉注射后肺外肿瘤相对少见的原因。在本通讯中，针对分别注入小鼠或大鼠门静脉的B16黑色素瘤和Walker 256细胞从肝到肺的转运，进一步研究了循环癌细胞“第一个器官处理”的概念。这两种细胞类型在尾静脉注射后在肺中都生长良好。
