肺转移瘤的转移前微环境与转移微环境

Pre-metastatic Niche and Metastatic Niche of Metastatic Lung Tumors

一个多世纪前Paget就肿瘤器官特异性转移现象提出了"种子与土壤"学说。时下研究热点集中在一些特殊因子介导的靶器官环境改造,肿瘤细胞归巢行为。有动物实验证实肺转移瘤形成前,肺部已发生大量炎症因子聚集。宿主靶器官的改变影响转移瘤形成的每一个步骤。Bethan Psaila与David Lyden针对这一土壤变化过程提出转移前微环境(pre-metastatic niche)及转移微环境(metastatic niche)假说,指出土壤的变化是转移瘤形成的保障。该假说提出后迅速引起肿瘤研究界轰动。研究这一系列细胞分子生物学的改变,有助于阐明肿瘤转移这一复杂的过程,为转移干预带来新的思路。

Steven Paget＇s ＂seed and soil＂ hypothesis for metastasis was a pivotal milestone in the study ofmalignant disease. Current views of cancer metastasis have centered on the intrinsic factors mediating preparation of the target organ and regulating the cell autonomous homing of tumor cells to the metastatic site. Many inflammatory cytokines in the lung provide an assembly platform for metastatic lesions, as shown by in vivo experimental models. New findings suggest that host cells within the target microenviroment play a key role in influencing each step of metastatic progression. Bethan Psaila and David Lyden have proposed a pre-metastatic niche and metastatic niche model to delineate the interactions of malignant cells with their microenvironment at the metastatic site. The niche model suggests that a suitably conducive microenvironment is essential in order for tumor cells to engraft and proliferate at secondary sites. It has quickly become the most influential hypothesis. Focusing on the cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to explain the events and to prevent metastasis at each step.