Nicolson G L, Poste G
Curr Probl Cancer. 1983 Jan;7(7):1-42. doi: 10.1016/s0147-0272(83)80005-1.
Recent findings that (1) individual tumor cells in a malignant lesion possess widely different metastatic properties and (2) metastases arise from specific subpopulations of metastatic tumor cells have profound implications for eventually understanding and treating metastatic diseases. These findings have also raised serious doubts concerning the appropriateness of many of the experimental approaches currently in use for studying metastasis. Diversity in metastatic phenotype among cells from the same tumor suggests that the usual analyses of tumor cell lines containing multiple heterogeneous subpopulations may not be fruitful. This is especially true for tumors where the metastatic subpopulations represent only an extremely small fraction of the total number of tumor cell subpopulations. In addition, the screening of potential antitumor and antimetastatic agents for their abilities to inhibit the growth of tumors containing widely heterogeneous subpopulations of metastatic and nonmetastatic cells may not be useful in predicting the efficacy of these treatments against metastases. New methodologies must be developed to isolate and characterize the specific cell subpopulations that possess the metastatic phenotype, with the reservation that careful attention must be paid to the stabilities of these malignant cell subpopulations, especially during long-term growth. Understanding the mechanism(s) controlling the rapid generation of phenotypic diversity in tumor subpopulations, and the regulation of subpopulation diversity during progressive growth of primary and metastatic lesions, is of fundamental importance in the design of experimental systems for studying the metastatic process, and eradicating metastases. This review and its companion, as well as our other recent reviews, have dealt with current information on cancer metastasis and where future efforts might be the most promising in discerning this complex process.
（1）恶性病变中的单个肿瘤细胞具有广泛不同的转移特性；（2）转移源自转移性肿瘤细胞的特定亚群。这些发现对于最终理解和治疗转移性疾病具有深远意义。这些发现也对目前用于研究转移的许多实验方法的适用性提出了严重质疑。同一肿瘤细胞之间转移表型的多样性表明，对包含多个异质亚群的肿瘤细胞系进行常规分析可能不会有结果。对于转移性亚群仅占肿瘤细胞亚群总数极小部分的肿瘤来说尤其如此。此外，筛选潜在的抗肿瘤和抗转移药物，以检测它们抑制含有广泛异质的转移性和非转移性细胞亚群的肿瘤生长的能力，可能无助于预测这些治疗对转移的疗效。必须开发新的方法来分离和表征具有转移表型的特定细胞亚群，但要注意必须仔细关注这些恶性细胞亚群的稳定性，尤其是在长期生长过程中。了解控制肿瘤亚群中表型多样性快速产生的机制，以及在原发性和转移性病变进行性生长过程中亚群多样性的调节，对于设计研究转移过程和根除转移的实验系统至关重要。本综述及其姊妹篇，以及我们最近的其他综述，都涉及了有关癌症转移的当前信息，以及未来在识别这一复杂过程方面哪些努力可能最有前景。
