Alterman A L, Fornabaio D M, Kim Y S, Stackpole C W
Department of Pathology, New York Medical College, Valhalla.
Invasion Metastasis. 1989;9(4):242-53.
B16 melanoma-derived cell lines and clones that initiate rapid-growing and nonmetastatic tumors in normal young (2-month-old) mice were previously shown to form slower-growing and highly metastatic tumors in normal mature or aged (greater than 10-month-old) mice. Similarly, slower tumor growth and enhanced metastasis occurred in young mice hyperimmunized against tumor-associated antigens. The metastatic characteristics of subcutaneous tumors initiated by one B16 melanoma clone, G3.26, were examined in normal young mice, normal mature mice, young mice immunized against G3.26 cells, and young mice maintained on a diet of 50% less food than usual. In normal young mice, tumors rarely disseminated viable lung metastases, even at very large sizes, and viable tumor cells were not detected in blood obtained by whole-body vascular perfusion. In contrast, tumors in mature, in immunized, and in calorie-restricted mice gave rise to visible lung metastases in 60-90% of mice, with dissemination beginning at relatively small tumor sizes. These tumors grew 27-78% slower than tumors in normal young mice, but in no case was expression of metastatic activity dependent on longer host survival. In all three experimental hosts, metastatic activity was transient and not expressed during subsequent growth of metastases in young mice. Different host mechanisms operating in mature, immune, and calorie-restricted mice were probably responsible for suppressing tumor growth. However, the consistent generation of metastatic activity under such diverse conditions suggests a common basis for promotion of metastasis, possibly related to intratumor environment alterations resulting from slower tumor growth.
先前研究表明，源自B16黑色素瘤的细胞系和克隆在正常年轻（2个月大）小鼠中会引发快速生长且不转移的肿瘤，但在正常成熟或老龄（超过10个月大）小鼠中则会形成生长较慢且具有高度转移性的肿瘤。同样，在针对肿瘤相关抗原进行过超免疫的年轻小鼠中，肿瘤生长也会减缓且转移增强。我们检测了由一个B16黑色素瘤克隆G3.26在正常年轻小鼠、正常成熟小鼠、针对G3.26细胞免疫的年轻小鼠以及食物摄入量比正常少50%的年轻小鼠中引发的皮下肿瘤的转移特性。在正常年轻小鼠中，即使肿瘤体积非常大，肿瘤也很少扩散形成可存活的肺转移灶，并且通过全身血管灌注获取的血液中未检测到存活的肿瘤细胞。相比之下，成熟小鼠、免疫小鼠和热量限制小鼠中的肿瘤在60 - 90%的小鼠中引发了可见的肺转移灶，转移在肿瘤相对较小时就开始了。这些肿瘤的生长速度比正常年轻小鼠中的肿瘤慢27 - 78%，但在任何情况下，转移活性的表达都不依赖于宿主更长的存活时间。在所有三种实验宿主中，转移活性都是短暂的，并且在年轻小鼠后续转移生长过程中未表达。成熟小鼠、免疫小鼠和热量限制小鼠中不同的宿主机制可能负责抑制肿瘤生长。然而，在如此多样的条件下一致产生转移活性表明存在促进转移的共同基础，可能与肿瘤生长减缓导致的肿瘤内环境改变有关。
