Modeling metastasis biology and therapy in real time in the mouse lung
Modeling metastasis biology and therapy in real time in the mouse lung
复制标题
DOI：
10.1172/jci40252
复制
发表时间：
2010-08-01
影响因子：
15.9
通讯作者：
Khanna, Chand
中科院分区：
文献类型：
--
作者：
Mendoza, Arnulfo;Hong, Sung-Hyeok;Khanna, Chand
肺转移仍然是癌症患者死亡的主要原因。改善患者治疗结果的机会需要新的方法来研究和观察转移进展的生物学。在这里，我们描述了一种离体肺转移试验（PuMA），其中表达GFP的癌细胞的转移进展，从单细胞到多细胞集落的形成，在小鼠肺微环境中进行了评估，在真实的时间长达21天。通过预测多种高转移和低转移人和小鼠癌细胞系的体内行为以及区分肺中最允许转移的肿瘤微环境，证实了该测定的生物学有效性。使用这种方法，我们提供了我们认为是肿瘤细胞与肺微环境基质成分相互作用的重要性的新见解。最后，通过其在转移进展期间的离散时间点的治疗评价中的使用，证明了该测定的转化效用。我们相信，这种检测系统是唯一能够推进我们的转移生物学和治疗策略的理解。
Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies.