1. ¹Ludwig Institute for Cancer Research, Post Office Box 2008 Royal Melbourne Hospital, Victoria 3050, Australia
2. ²Department of Surgery, The Royal Melbourne Hospital, University of Melbourne, Parkville 3050, Victoria, Australia

Correspondence: Associate Professor MG Achen or Associate Professor SA Stacker, E-mails: Marc.achen@ludwig.edu.au, Steven.stacker@ludwig.edu.au

Received 27 January 2006; Revised 20 March 2006; Accepted 29 March 2006; Published online 25 April 2006.

Abstract

Recent studies involving animal models of cancer and clinicopathological analyses of human tumours suggest that the growth of lymphatic vessels (lymphangiogenesis) in or nearby tumours is associated with the metastatic spread of cancer. The best validated molecular signalling system for tumour lymphangiogenesis involves the secreted proteins vascular endothelial growth factor-C (VEGF-C) and VEGF-D that induce growth of lymphatic vessels via activation of VEGF receptor-3 (VEGFR-3) localised on the surface of lymphatic endothelial cells. In this review, we discuss the evidence supporting a role for this signalling system in the spread of cancer and potential approaches for blocking this system to prevent tumour metastasis.