Oral Presentation 6th Australian Health and Medical Research Congress 2012

The Molecular Control of Vascular Remodelling (#2)

Steven Stacker 1 , Steve Williams 1 2 , Rae Farnsworth 1 2 , Tara Kanezis 1 , Ramin Shayan 1 , Sophie Pacquet-Fifeild 1 , Natalia Davydova 1 , Sidney Levy 1 2 , Nicole Harris 1 2 , Carol Caeser 1 , Sally Roufail 1 , You-Fang Zhang 1 , Marc G Achen 1
  1. Tumour Angiogenesis Program, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  2. Department of Surgery, University of Melbourne, Parkville, VIC, Australia

The remodelling of blood and lymphatic vessels is a critical aspect of human pathology and is associated with inflammation, infection and malignancy. The discovery and characterisation of the lymphangiogenic growth factors vascular endothelial growth factor-C (VEGF-C) and VEGF-D and of their receptor on lymphatic endothelial cells, VEGFR-3, has provided an understanding of the molecular mechanisms controlling the growth of lymphatic vessels.  Our growing understanding of the molecular mechanisms controlling the blood and lymphatic systems has led to the isolation and characterisation of numerous families of growth factors and receptors that in part control the growth and remodelling of the vasculature.

 To gain a further understanding of how complex signalling networks in endothelial cells work together to generate the growth, differentiation and remodelling of lymphatic vessels, we have established approaches to identify novel, functionally important genes in lymphatic endothelial cells and markers of lymphatic subsets. Using microarray expression analysis of purified lymphatic endothelial cell populations from vessels within tumour-involved lymph nodes and collecting lymphatic vessels carrying metastatic tumour cells we have identified two novel pathways for modulating tumour metastasis (Farnsworth et al., 2011; Karnezis et al., 2012).

 Furthermore we have used genome-wide siRNA screening approaches to identify molecules which are important for the movement and differentiation of lymphatic endothelial cells. These screens are allowing us to map key signalling networks for the control of vessel remodelling in the lymphatics.

  1. Farnsworth RH, Karnezis T, Shayan R, et al. A role for bone morphogenic protein-4 in vascular endothelial growth factor-D mediated tumor growth, metastasis and vessel remodelling. Cancer Res 2011; 71: 6547-6557.
  2. Karnezis T, Shayan R, Caesar C, et al. VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell 2012; 21: 181-195.