Role of incipient angiogenesis in cancer metastasis

Metastasis is the primary cause of mortality in cancer patients. Angiogenesis is intimately involved in metastasis at the site of entry of tumor cells into the vasculature and at the site of eventual metastasis growth. In this commentary, we review current paradigms regarding angiogenesis in metastatic sites. Recent discoveries challenge some of the existing paradigms. Significant prior data suggest that successful formation of metastases requires: 1) angiogenesis in the primary tumor site; 2) downregulation of cohesive molecules and tumor cell increased motility, resulting in invasion into neovessels; 3) tumor cell embolism; 4) arrest and attachment in capillary beds of distant organs; 5) extravasation and proliferation in the organ parenchyma; and 6) re-establishment of angiogenesis when the tumor reaches > 1-2 mm in size [1]. While most recent data largely confirm the aforementioned sequence of events, a few reports have revealed new knowledge about the earliest phases of angiogenesis of metastases. Of particular importance has been the ability to create tumor cell lines that are stably transfected with reporter genes, such as green fluorescence protein. With these tools it is now literally possible to monitor tumor formation from a single cell [2-7].