Figure 2.

The successful metastasis of a cancer cell from the primary tumor to a distant site requires several steps, each of which necessitates unique cellular characteristics. Expression of PLD has been implicated in supporting each of these processes as indicated by arrows. The effects of PLD in regulating actin polymerization (green arrows), matrix metalloproteinase secretion (red arrows), and platelet activation (blue arrows) are particularly important to the process, although additional mechanisms also contribute. Once initiating tumor cells transform and grow to form the primary tumor, cells must stimulate angiogenesis to maintain nutrients and provide access to the lymphovascular system. Cancer cells must then reduce adhesion to neighboring cells to detach and degrade surrounding extra cellular matrix (ECM). This provides a path for migration cells to invade neighboring stromal cells and reach vasculature. Cancer cells must then intravasate into circulation by opening endothelial cells or crossing at leaky points. When circulating in the blood, cancer cells activate platelets to form protective coverings that prevent immune cell killing and promote trapping in the narrow capillaries of distant organs. The cancer cells must then extravasate and proliferate in the new location, which requires adaptations to new stroma, nutrients, and growth factors.