[Tumor metastasis. Molecular principles and therapeutic options]

Metastasis formation is a multistep process that requires tumor cells to progress through many different stages. One of the first steps is a disturbance of the epithelial integrity through a decrease in intercellular homotypic adhesion. Proteolysis of the extracellular matrix, as well as increased locomotion, leads to intravasation and dissemination of the tumor cells. In the target organs metastasizing cells adhere to the endothelium, extravasate and form metastases. Finally, neoangiogenesis is required for the initiation as well as the growth of the metastases, providing the tumor cells with both nutritive agents and growth factors. This leads to the conclusion that anti-proteolytic and anti-angiogenic substances could provide effective therapeutic approaches for the control of metastatic growth. Whether or not this goal can be accomplished by synthetic or endogenous drugs must still be demonstrated by basic and definitive clinical research.