Poste G
Cancer Metastasis Rev. 1982;1(2):141-99. doi: 10.1007/BF00048224.
Identification of the cellular and subcellular alterations responsible for the metastatic behavior of malignant tumor cells and development of reliable screening programs for detecting new therapeutic agents for improved treatment of metastatic disease both depend crucially on the availability of experimental systems that can serve as relevant models of human cancer. Recent advances in our understanding of the pathogenesis of cancer metastasis have raised serious doubts about the usefulness of many of the experimental approaches that have long been used in the study of metastasis. Recent findings showing that metastases are caused by specific subpopulations of metastatic tumor cells, and that not all cells in a malignant primary tumor possess metastatic properties, are of profound importance for experimental efforts to understand the mechanism of metastatic phenotype among cells from the same tumor means that the traditional, and widely used, approach of analyzing primary tumors and cultured cell lines containing multiple, phenotypically heterogeneous, subpopulations of cells may provide little or no insight into the properties of the metastatic subpopulations, particularly if they represent only a minor fraction of the entire population. Similarly, the practice of screening potential therapeutic modalities for their ability to reduce the mass and/or growth rate of a primary tumor may be inadequate in predicting the responsiveness of metastatic lesions. Solution of these problems requires that new methods must be devised to isolate and characterize the specific subpopulations of tumor cells endowed with metastatic potential. In addition, knowledge of how the extraordinary phenotypic diversity found in tumor cell subpopulations from the same tumor is generated and how subpopulation diversity is regulated during progressive growth of both the primary tumor and its metastases are of fundamental importance if we are to design meaningful experimental systems for studying the metastatic process. This article reviews our current understanding of these complex issues and their implications for the experimental analysis of the malignant phenotype. The merits and shortcomings of different experimental systems are discussed in detail together with the identification of areas in which new experimental strategies and models are now needed.'
确定导致恶性肿瘤细胞转移行为的细胞和亚细胞改变，以及开发可靠的筛选程序以检测用于改善转移性疾病治疗的新治疗药物，这两者都至关重要地依赖于能够作为人类癌症相关模型的实验系统的可用性。我们对癌症转移发病机制理解的最新进展，对长期以来用于转移研究的许多实验方法的实用性提出了严重质疑。最近的研究结果表明，转移是由转移性肿瘤细胞的特定亚群引起的，并且并非恶性原发性肿瘤中的所有细胞都具有转移特性，这对于理解同一肿瘤细胞中转移表型机制的实验工作具有深远意义，意味着传统且广泛使用的分析原发性肿瘤和包含多个表型异质细胞亚群的培养细胞系的方法，可能对转移亚群的特性提供很少或没有见解，特别是如果它们仅占整个群体的一小部分。同样，筛选潜在治疗方式以降低原发性肿瘤质量和/或生长速率的能力，在预测转移性病变的反应性方面可能并不充分。解决这些问题需要设计新的方法来分离和表征具有转移潜力的肿瘤细胞特定亚群。此外，如果我们要设计有意义的实验系统来研究转移过程，了解同一肿瘤的肿瘤细胞亚群中发现的非凡表型多样性是如何产生的，以及在原发性肿瘤及其转移的渐进生长过程中亚群多样性是如何调节的，具有根本重要性。本文综述了我们目前对这些复杂问题的理解及其对恶性表型实验分析的影响。详细讨论了不同实验系统的优缺点，并确定了现在需要新实验策略和模型的领域。
