Aabo K, Vindeløv L L, Spang-Thomsen M
University Institute of Pathological Anatomy, University of Copenhagen, Denmark.
Eur J Cancer. 1995;31A(2):222-9. doi: 10.1016/0959-8049(94)00434-7.
Clonal evolution of neoplastic cells during solid tumour growth leads to the emergence of new tumour cell subpopulations with diverging phenotypic characteristics which may alter the behaviour of a malignant disease. Cellular interaction was studied in mixed xenografts in nude mice and during in vitro growth of two sets of small cell lung cancer (SCLC) subpopulations (54A, 54B and NYH, NYH2). The tumour cell lines differed in cellular DNA content enabling flow cytometric DNA analysis (FCM) to be used to monitor changes in the fractional composition of the mixed cell populations. The progeny clone 54B was found to dominate the parent 54A clone when grown as mixed subcutaneous xenografts in nude mice, whereas no dominance was exerted during in vitro growth. The in vivo dominance could not be explained by differences in growth kinetics between the two tumour cell lines, and the interaction was not dependent on 54B being in excess in mixed tumours. The dominance was dependent on close in vivo contact as no remote effect on the growth of 54A was found when the dominating 54B cells were growing in the opposite flank of tumour-bearing mice. Irradiation inactivated 54B cells were unable to exert the dominating effect, indicating that the interaction required viable and proliferating cells. Clonal dominance was not found in mixed NYH-NYH2 tumours indicating that the dominance mechanism(s) may not always be operational between subpopulations in heterogeneous tumours. Recognition of interaction between tumour cell populations may result in a better understanding of the behaviour of heterogeneous human malignancies.
实体瘤生长过程中肿瘤细胞的克隆进化导致具有不同表型特征的新肿瘤细胞亚群出现，这可能改变恶性疾病的行为。在裸鼠混合异种移植瘤以及两组小细胞肺癌（SCLC）亚群（54A、54B和NYH、NYH2）的体外生长过程中研究了细胞间相互作用。这些肿瘤细胞系在细胞DNA含量上存在差异，使得能够利用流式细胞术DNA分析（FCM）来监测混合细胞群体组成比例的变化。当作为混合皮下异种移植瘤在裸鼠体内生长时，子代克隆54B被发现主导亲本54A克隆，而在体外生长过程中则没有出现主导现象。体内的主导现象无法用两种肿瘤细胞系生长动力学的差异来解释，并且这种相互作用并不依赖于混合肿瘤中54B过量存在。这种主导作用依赖于体内的紧密接触，因为当占主导地位的54B细胞在荷瘤小鼠的对侧侧翼生长时，未发现对54A生长有远程影响。经辐射灭活的54B细胞无法发挥主导作用，这表明这种相互作用需要有活力且能增殖的细胞。在NYH - NYH2混合肿瘤中未发现克隆主导现象，这表明在异质性肿瘤的亚群之间，主导机制可能并非总是起作用。认识肿瘤细胞群体之间的相互作用可能会更好地理解异质性人类恶性肿瘤的行为。
