Mager D, Mak T W, Bernstein A
Nature. 1980 Dec 11;288(5791):592-4. doi: 10.1038/288592a0.
Neoplastic cells are characterized by partial or total autonomy from the interactions that regulate the behaviour of normal cells in the intact animal. Despite the role of the host cellular environment in governing the proliferation and differentiation of both normal and malignant cells, little is known about these host factors. The characterization of host genes that influence both normal cellular processes, as well as susceptibility to tumour induction, is one approach to identifying such factors. Mice carrying two recessive mutations at the steel (Sl) locus have an environmental defect that affects both normal haematopoietic stem cell function as well as susceptibility to Friend leukaemia virus. In this study, we have used Sl/sld mice to examine whether malignant transformation by this RNA tumour virus results in a population of cells capable of proliferating even in the defective cellular microenvironment of Sl/sld mice. We report here that late after infection, the leukaemic spleens of Friend virus-infected mice contain cells which, unlike normal haematopoietic stem cells, are able to form macroscopic spleen colonies in irradiated mice of genotype Sl/Sld. This observation forms the basis for the first in vivo colony assay for leukaemic cells transformed by Friend virus.
肿瘤细胞的特征是部分或完全不受调节完整动物体内正常细胞行为的相互作用的影响。尽管宿主细胞环境在控制正常细胞和恶性细胞的增殖与分化中发挥作用,但对这些宿主因素却知之甚少。鉴定影响正常细胞过程以及肿瘤诱导易感性的宿主基因是识别此类因素的一种方法。在钢(Sl)位点携带两个隐性突变的小鼠存在一种环境缺陷,这种缺陷既影响正常造血干细胞功能,也影响对Friend白血病病毒的易感性。在本研究中,我们使用Sl/sld小鼠来检验这种RNA肿瘤病毒引起的恶性转化是否会产生即使在Sl/sld小鼠有缺陷的细胞微环境中也能增殖的细胞群体。我们在此报告,感染后晚期,Friend病毒感染小鼠的白血病脾脏中含有一些细胞,这些细胞与正常造血干细胞不同,能够在基因型为Sl/Sld的受辐照小鼠中形成肉眼可见的脾脏集落。这一观察结果构成了对Friend病毒转化的白血病细胞进行首次体内集落测定的基础。