We use clinically relevant xenograft models to study the process of metastasis. We have developed a variety of models, so that we can examine the process across various tumor entities.

We explain systemic metastasis formation with a pathophysiological model that all solid hematogenous tumor entities have in common: all the tumor cells in the blood have to communicate with the cellular lining of blood vessels, the endothelium at the destination of metastases. The tumor cell must adhere to the endothelium and in the next step migrate into the tissue. Otherwise the tumor cells perish in bloodstream.

To do so, the tumor cells use similar molecular mechanisms that are used normally by the white blood cells (leukocytes). Leukocytes migrate from the bloodstream into inflamed tissue. In this case, they use a number of different cell adhesion molecules, which are also used by the tumor cells for the adhesion to the endothelium.

First, the leukocyte/tumor cells adhere via endothelial selectins. Selectins are carbohydrate-binding proteins on the cell surface of endothelial cells that recognize glycan structures on leukocytes/tumor cells. After selectin binding there are several other cell adhesion molecules involved in the firm binding including integrins, all of which play an important functional role in the adhesion and migration of cancer cells. Since these molecules are activated in a specific order, one speaks of an adhesion cascade.

Metastasis formation is so complex, because the molecules are redundant and are partly members of large protein molecule families. Within these families, several molecules can substitute for each other. These redundancies and substitutions make it difficult to get a complete understanding of adhesion as a key step in metastasis.

To understand the significance of individual molecules we knock out selected adhesion molecules with the aim to disrupt the adhesion cascade of metastasis formation. Sometimes we also need to disable multiple molecules to be successful.