Henderson J S
J Exp Med. 1967 Jan 1;125(1):71-89. doi: 10.1084/jem.125.1.71.
The cells of a mouse mammary cancer were obtained with enzymes in suspensions which could be filtered to exclude all which were not single and most which were already dead. Heavy suspensions of these individual cells were plated over the dorsal subcutaneous expanses of female weanling mice where they implanted and grew to form coalescent tumors covering the back more or less entirely. Sparser suspensions, similarly plated (a) gave rise to fewer tumors, and (b) gave rise to tumors reaching measurable size later. These two consequences of sparser plating left room for the testing of adjuvators to transplantation. Adjuvator effects were obtained by splitting the subcutaneous expanses beforehand and by injecting liver along with the plated cells. Through 28 plated generations over 4 yr the tumor maintained completely stable, morphological heterogeneity. These findings with a complex tumor indicate strongly that its heterogeneity comes not from repeated cellular mutation late in its development, but from diverse potentiality to give rise to cells of specific and differing character, inherent in its individual cells at the time of its multicellular origin.
用酶从悬浮液中获取小鼠乳腺癌细胞，该悬浮液经过过滤可排除所有非单个细胞以及大多数已死亡的细胞。将这些单个细胞的重悬液接种到雌性断奶小鼠的背部皮下区域，细胞在那里植入并生长，形成或多或少完全覆盖背部的融合肿瘤。同样接种较稀疏的悬浮液（a）产生的肿瘤较少，（b）产生的肿瘤达到可测量大小的时间较晚。接种较稀疏的这两个结果为测试移植佐剂留出了空间。通过预先分割皮下区域并在接种细胞时注射肝脏获得了佐剂效果。在4年的28代接种过程中，肿瘤保持了完全稳定的形态异质性。这些关于复杂肿瘤的发现有力地表明，其异质性并非来自肿瘤发育后期的反复细胞突变，而是来自其多细胞起源时单个细胞中固有的产生具有特定和不同特征细胞的多种潜能。
