The role of immune cells and the inflammatory response in tumor cell metastasis
In recent years, there has been a marked improvement in the clinical classification of individual cancer sub-types based on their detailed genetic and pathophysiological analysis. While this has had a tremendous impact on determining patient diagnosis, current treatments used to block the spread of tumour cells have largely been unsuccessful, and metastasis (the spread of tumour cells from a primary tumour to secondary sites), remains responsible for 90 percent of cancer deaths. Notably, the number of cancer cells that have the capacity to reach the bloodstream correlates with primary tumour size, and when diagnosed with cancer, patients can expect to have between 100,000 and more than one million circulating tumour cells in their blood. This apparent inefficiency of tumour cells to get out of the bloodstream and proliferate may be an important avenue for therapy, as maintaining and/or enhancing this inefficiency could be a key step in blocking the spread of cancer. Recently, Spencer Freeman has been investigating this possibility. His research has provided general information on how tumour cells adhere to and migrate out of the blood vasculature, and he has identified Rap1 and integrin as critical regulators of tumour cell adhesion. Moreover, Mr. Freeman and colleagues have been able to block this pathway using antibodies and genetic approaches, which has reduced the ability of tumour cells to adhere to and migrate out of the vasculature in vitro as well as in animal models. In his current research project, Mr. Freeman is investigating the underlying mechanism, in particular the signalling events, which mediate communication between tumour cells, circulating blood leukocytes and vascular endothelial cells. The results of his research will improve our understanding of the genetic axis and physical steps that tumour cells use in order to first colonize distant sites. In turn, this knowledge may lead to improved cancer treatments against metastatic disease.