Extravasation of leukocytes in comparison to tumor cells

The extravasation is a multi-step process of the emigration of cells from the blood stream into the tissue. The most prominent types of extravasating cells are leukocytes, i.e. T lymphocytes, natural killer (NK) cells, neutrophil granulocytes and monocytes. These cells have to leave the blood vessels in order to reach tissue sites of inflammation, infection or injury. But not only the emigrating cells, the vascular endothelium takes actively part in the extravasation process, too. It has to deliver certain localization signals, so that the leukocytes know where and when to emigrate. Therefore, the endothelium changes dynamically its architecture including receptor expression and cell-cell contacts. In contrast to the important and physiological extravasation of leukocytes, tumor cells are disseminated by the circulation through the body during hematogenic metastasis development. Akin to leukocytes, tumor cells do not randomly leave the blood vessels, but are guided by certain signals that are also delivered by the vascular endothelium. Earliest observations on this have been documented more than hundred years ago by Paget, who regarded in his theory on breast cancer metastasis the cancer cells as a seed that can only grow at certain sites of the body, which he considered as the soil [1]. Balkwill and Mantovani worded the assumption that tumor cells might use chemokine gradients to spread around the body [2], therefore, tumor cells and leukocytes might use similar localization signals. The stromal cell-derived factor (SDF)-1α is such a chemokine, which is expressed in organs that are the first destination of breast cancer metastases [3]. We have elaborated this hypothesis on localization signals: ligands to G protein-coupled receptors (GPCRs), which are chemokines and neurotransmitters as well, might chemotactically guide tumor cells to their destination of metastasis formation [4].The extravasation process is in principle divided into three sequential steps regardle