Lymphatics, cancer and zebrafish

Abstract

Many solid tumors are known to metastasize through the lymphatic vasculature. This process is facilitated by the generation of new lymphatic vessels (tumor lymphangiogenesis) and also by the remodelling of existing lymphatics. Together these processes enable the spread of tumor cells to distant sites. Currently our understanding of tumor lymphangiogenesis has been informed from mouse tumor models and from studies of developmental lymphangiogenesis. Since the discovery of bona fide lymphatic vessels in zebrafish in 2006, zebrafish have become a well-established model of developmental lymphangiogenesis. The attributes that make zebrafish such an important model of blood vessel development—the ability to live image developing vessels, genetic tractability and the conserved nature of development—also make fish an attractive model of lymphatic vessel development. In particular, zebrafish have made important contributions to our understanding of the processes of lymphatic vessel sprouting from veins and the mechanisms by which lymphatic precursors remodel into mature vessels. To date, zebrafish have not been used to directly model tumor lymphangiogenesis. In this chapter we will summarise the contributions zebrafish have made to our understanding of lymphangiogenesis and investigate the possibilities of combining zebrafish transgenic cancer lines or tumor transplantation models with existing lymphatic reporter lines, which could provide valuable insights into the process of tumor-induced lymphangiogenesis. In addition the utility of using the zebrafish lymphatic model as a platform to screen and develop novel anti-lymphatic therapeutics will also be discussed.