Chemokines in tumor-associated angiogenesis.

Tumor growth is dependent on several key factors. Apart from immune escape and an efficient blockade of apoptotic signals, tumors require oxygen and nutrients to grow past a diameter of 2 microm. Therefore, it is of vital importance for the tumor to facilitate tumor-associated angiogenesis, e.g., the de novo formation of new blood vessels. In addition to established and key angiogenic factors, such as vascular endothelial growth factor, chemokines, a superfamily of cytokine-like proteins that bind to seven transmembrane-spanning G-protein-coupled receptors, have been associated with angiogenesis under homeostatic conditions. Chemokines were initially identified as key factors that control the directional migration of leukocytes, stem cells and cancer cells in vitro and which critically regulate their trafficking in vivo. Recently their role in establishing a favorable microenvironment for tumor-associated angiogenesis, a process that requires complex bidirectional interactions of the tumor and associated vessels, has been the focus of research. Chemokine-promoted angiogenesis not only facilitates tumor growth by supplying nutrients and oxygen but it is also a prerequisite to tumor metastasis. Hence, the pharmacologic control of tumor angiogenesis presents a promising strategy for novel anticancer therapeutics. Here, we discuss the current pathogenetic concepts of tumor-associated angiogenesis in the context of chemokines and their receptors and highlight promising therapeutic strategies.