Extravasation of leukocytes in comparison to tumor cells

Abstract

The multi-step process of the emigration of cells from the blood stream through the vascular endothelium into the tissue has been termed extravasation. The extravasation of leukocytes is fairly well characterized down to the molecular level, and has been reviewed in several aspects. Comparatively little is known about the extravasation of tumor cells, which is part of the hematogenic metastasis formation. Although the steps of the process are basically the same in leukocytes and tumor cells, i.e. rolling, adhesion, transmigration (diapedesis), the molecules that are involved are different. A further important difference is that leukocyte interaction with the endothelium changes the endothelial integrity only temporarily, whereas tumor cell interaction leads to an irreversible damage of the endothelial architecture. Moreover, tumor cells utilize leukocytes for their extravasation as linkers to the endothelium. Thus, metastasis formation is indirectly susceptible to localization signals that are literally specific for the immune system. We herein compare the extravasation of leukocytes and tumor cells with regard to the involved receptors and the localization signals that direct the cells to certain organs and sites of the body.

Figure 1

Receptors involved in the rolling of leukocytes and tumor cells. The endothelium is shown in green, leukocytes in blue and tumor cells in red.

Figure 2

Receptors involved in the adhesion of leukocytes and tumor cells to endothelial cells. The endothelium is shown in green, leukocytes in blue and tumor cells in red.

Figure 3

Transmigration of leukocytes through endothelium. Receptors involved in the paracellular or junctional route are shown on the left side, receptors involved in the transcellular route are shown on the right side. The endothelial cells are shown in green, the leukocytes in blue.