Nicolson G L
Department of Tumor Biology, University of Texas M. D. Anderson Hospital and Tumor Institute, Houston 77030.
Cancer Metastasis Rev. 1988 Jun;7(2):143-88. doi: 10.1007/BF00046483.
The locations of distant secondary tumors in many clinical cancers and animal tumors are nonrandom, and their distributions cannot be explained by simple anatomical or mechanical hypotheses based on the simple lodgment or trapping of tumor cell emboli in the first capillary bed encountered. Evidence from certain experimental tumor systems supports Paget's 'seed and soil' hypothesis on the nonrandom distributions of metastases, in which the unique properties of particular tumor cells ('seeds') and the different characteristics of each organ microenvironment ('soil') collectively determine the organ preference of metastasis. Experimentally, differential tumor cell adhesion to organ-derived microvessel endothelial cells and organ parenchymal cells, differential invasion of basement membranes and organ tissues, and differential responses to organ-derived growth-stimulatory and -inhibitory factors all appear to be important determinants in explaining the organ preference of metastasis. Each tumor system may achieve organ specificity because of its own unique set of multiple metastasis-associated properties and responses to host microenvironments. As neoplasms progress to more highly malignant states multisite metastases are more likely and organ-specific metastases may be masked or circumvented owing to stochastic events, tumor cell diversification, host selection processes, and increased production of tumor autocrine molecules that may modulate adhesion, invasion, growth, and other properties important in metastasis. The importance of each of these properties, however, appears to vary considerably among different metastatic tumor systems. These and other tumor cell and host properties may eventually be used to predict and explain the unique metastatic distributions of certain human malignancies.
在许多临床癌症和动物肿瘤中，远处继发性肿瘤的位置并非随机，其分布无法用基于肿瘤细胞栓子在首个遇到的毛细血管床中简单滞留或截留的简单解剖学或机械学假说来解释。来自某些实验性肿瘤系统的证据支持佩吉特关于转移灶非随机分布的“种子与土壤”假说，即特定肿瘤细胞（“种子”）的独特特性与每个器官微环境（“土壤”）的不同特征共同决定了转移的器官偏好性。在实验中，肿瘤细胞与器官来源的微血管内皮细胞和器官实质细胞的差异性黏附、对基底膜和器官组织的差异性侵袭以及对器官来源的生长刺激和抑制因子的差异性反应，似乎都是解释转移器官偏好性的重要决定因素。每个肿瘤系统可能因其自身独特的一组与转移相关的多种特性以及对宿主微环境的反应而实现器官特异性。随着肿瘤发展到更高的恶性状态，多部位转移更有可能发生，并且由于随机事件、肿瘤细胞多样化、宿主选择过程以及肿瘤自分泌分子产量增加（这些分子可能调节黏附、侵袭、生长以及转移中重要的其他特性），器官特异性转移可能会被掩盖或规避。然而，这些特性中的每一个的重要性在不同的转移性肿瘤系统中似乎有很大差异。这些以及其他肿瘤细胞和宿主特性最终可能用于预测和解释某些人类恶性肿瘤独特的转移分布情况。
