[The metastatic niche. Mechanisms and prognostic implications]

Disseminated tumor cells require a special microenvironment to form metastases. This metastatic niche is organ specific and forms prior to the establishment of visible metastases. The niche is characterized by vascular remodeling and bone marrow-derived cells which have migrated into it. Studies by other groups and our own results have already shown that intranodal lymphangiogenesis is an important prerequisite for regional lymph node metastases in rectal cancer patients, and can be used as a prognostic marker for progression-free survival. Niche cells such as endothelia secrete factors that attract tumor and bone marrow-derived cells. CXCL12 is one of these factors. CXCL12 activates the CXCR4 chemokine axis and induces migration along its gradient. Several factors, such as hypoxia, have been described to regulate CXCR4 function and surface expression on tumor cells. Low molecular weight agents have been used to block CXCR4 activation. This review focuses on the function and regulation of CXCR4 and its ligand CXCL12 in metastases formation. It also discusses potential options for therapeutic blockage.