STEPS IN TUMOR-METASTASIS - NEW CONCEPTS FROM INTRAVITAL VIDEOMICROSCOPY

Metastases are responsible for the majority of failures in cancer trea tment. Clarifying steps in metastasis and their molecular mechanisms w ill be important for the development of anti-metastasis therapeutic st rategies. 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 dev eloped an intravital videomicroscopy (IVVM) procedure to make such obs ervations possible. Results from IVVM are providing us with new concep tual understanding of the metastatic process, as well as the nature an d timing of the contributions of molecules implicated in metastasis (e .g. adhesion molecules and proteinases). Our findings suggest that ear ly steps in metastasis, including hemodynamic destruction and extravas ation, may contribute less to metastatic inefficiency than previously believed. Instead, our results suggest that the control of post-extrav asation growth of individual cancer cells is a significant contributor to metastatic inefficiency. Thus, this stage may be an appropriate ta rget for design of novel strategies to prevent metastases.