Clonal interaction in tumours
Clonal interaction in tumours
复制标题
肿瘤中的克隆相互作用
作者：
Michael Woodruff;J. Ansell;G. Forbes;J. Gordon;D. Burton;H. Micklem
癌症的发展取决于至少一个转化细胞克隆的出现。一种用于研究人类肿瘤是否是单克隆性的方法依赖于两种形式的葡萄糖-6-磷酸脱氢酶(G-6-PD)1杂合子女性正常组织中的嵌合体。这种嵌合体是由于所有体细胞中一条X染色体失活的结果，不应该存在于单克隆体中。在野鼠身上发现了一种X编码的磷酸甘油酸激酶(PGK-1)的电泳变异体(A)，它不同于在普通实验室小鼠品系中发现的(B)形式。3据报道，在野鼠和实验室饲养的小鼠的杂交后代中，化学诱导的纤维肉瘤表达这两种酶的表型，但这两种酶都在肿瘤细胞中表达的结论仅基于形态证据。对一种或另一种同种异型酶纯合的小鼠组织相容亚系的发展使在实验条件下研究肿瘤的克隆组成成为可能，在这种条件下，可以通过移植来验证亚群细胞的肿瘤状态。我们现在报道的实验证实，小鼠纤维肉瘤通常是多克隆的，表明在组织培养和移植到同种宿主上时，克隆成分可能会发生显著变化。这些变化可能反映了肿瘤分化亚群生长动力学的变化。克隆的亚系比未克隆的肿瘤细胞群体更不容易移植，一些亚系比其他亚系更不容易移植；这表明在移植时选择了抵抗宿主攻击的亚系，或者一些亚系需要其他亚系的合作才能存活。我们推测，克隆成分的变化也发生在肿瘤的发展、转移和复发过程中。
The development of cancer is contingent on the emergence of at least one clone of transformed cells. One method used to investigate whether human tumours are monoclonal depends on the mosaicism in the normal tissues of women heterozygous for the two forms of the enzyme glucose-6-phosphate dehydrogenase (G-6-PD)1. This mosaicism results from the inactivation of one X chromosome in all somatic cells and should not exist in a monoclonal population. Following the discovery2 in feral mice of an electrophoretic variant (A) of the X-coded enzyme phosphoglycerate kinase (PGK-1) which differs from the form (B) found in common laboratory mouse strains it was reported3 that fibrosarcomas induced chemically in hybrids of feral and laboratory-bred mice expressed both enzyme phenotypes, but the conclusion that both were expressed by neoplastic cells was based solely on morphological evidence. The development of histocompatible substrains of mice homozygous for one or other alloenzyme has made it possible to study the clonal composition of tumours under experimental conditions in which the neoplastic status of subpopulations of cells can be verified by transplantation. The experiments we now report, while confirming that murine fibrosarcomas are often pleoclonal, show that the clonal composition may change markedly during tissue culture and on transplantation to con-genie hosts. These changes presumably reflect changes in the growth kinetics of differentiating subpopulations of the tumour. Cloned sublines are less readily transplantable than uncloned tumour cell populations, and some sublines are less readily transplantable than others; this suggests that sublines resistant to a host's attack are selected on transplantation or that some sublines require the cooperation of others to survive. We postulate that changes in clonal composition occur also during tumour development, metastasis and recurrence.