Chambers A F, MacDonald I C, Schmidt E E, Koop S, Morris V L, Khokha R, Groom A C
Department of Oncology, University of Western Ontario, London, Canada.
Cancer Metastasis Rev. 1995 Dec;14(4):279-301. doi: 10.1007/BF00690599.
Metastases are responsible for the majority of failures in cancer treatment. Clarifying steps in metastasis and their molecular mechanisms will be important for the development of anti-metastasis therapeutic strategies. Considerable progress has been made in identifying molecules involved in metastasis. However, because of the nature of assays that have been available, conclusions about steps in metastasis and their molecular bases have been drawn primarily from inference. In order to complete the picture of how metastases form, a technique is needed to directly watch the process in vivo as it occurs over time. We have developed an intravital videomicroscopy (IVVM) procedure to make such observations possible. Results from IVVM are providing us with new conceptual understanding of the metastatic process, as well as the nature and timing of the contributions of molecules implicated in metastasis (e.g. adhesion molecules and proteinases). Our findings suggest that early steps in metastasis, including hemodynamic destruction and extravasation, may contribute less to metastatic inefficiency than previously believed. Instead, our results suggest that the control of post-extravasation growth of individual cancer cells is a significant contributor to metastatic inefficiency. Thus, this stage may be an appropriate target for design of novel strategies to prevent metastases.
转移是癌症治疗失败的主要原因。阐明转移过程中的步骤及其分子机制对于抗转移治疗策略的开发至关重要。在识别参与转移的分子方面已经取得了相当大的进展。然而，由于现有检测方法的性质，关于转移步骤及其分子基础的结论主要是通过推断得出的。为了全面了解转移瘤是如何形成的，需要一种技术来直接观察体内随着时间推移发生的转移过程。我们已经开发了一种活体视频显微镜（IVVM）程序，使这种观察成为可能。IVVM的结果为我们提供了对转移过程的新的概念性理解，以及与转移相关的分子（如粘附分子和蛋白酶）的作用性质和时间。我们的研究结果表明，转移的早期步骤，包括血液动力学破坏和外渗，对转移效率低下的影响可能比以前认为的要小。相反，我们的结果表明，控制单个癌细胞外渗后的生长是转移效率低下的一个重要因素。因此，这个阶段可能是设计预防转移新策略的合适靶点。
