Chemokines: Angiogenesis and Metastases in Lung Cancer

Summary

Non-small cell lung cancer (NSCLC) growth, angiogenesis, invasion, and metastases to specific organs is dependent on an orchestrated series of events that include: cellular transformation; establishment of a pro-angiogenic environment; tumour cell proliferation, invasion and entry into the circulation; and tumour cell trafficking and metastatic tumour growth in specific organs based on the concept of Paget's theory of ‘seed and soil’ related to homing of tumour cells to a specific organ. The events that destine a tumour cell to invade and metastasize to distant organs are analogous to leukocyte trafficking. Chemokines have had an increasingly important role in mediating the homing of leukocytes under both conditions of homeostasis and inflammatory/immunological responses. Recently, the biology of chemokines has extended beyond their role in mediating leukocyte trafficking. Specifically, CXC chemokines have been found to be important in the regulation of angiogenesis, and in promoting tumour cell migration and organ-specific metastases. Data will be presented to highlight the importance of CXC chemokine ligands and receptors in mediating NSCLC tumour-associated angiogenesis, ‘immunoangiostasis’, and organ specific metastases. These findings may ultimately lead to clinical strategies to attenuate the pathobiology of CXC chemokines in promoting NSCLC tumour growth and metastases.