Associate Professor and Senior Research Fellow, The National Health and Medical Research Council of Australia
Joint-Head of the Angiogenesis Laboratory, Ludwig Institute for Cancer Research
Melbourne Tumour Biology Branch,
Post Office Royal Melbourne Hospital,
Parkville, Victoria 3050, Australia
Phone: (61-3) 9341 3155
Fax: (61-3) 9341 3107
Email: marc.achen@ludwig.edu.au
Research Interest
I study the molecular mechanisms controling the growth of blood vessels (hemangiogenesis) and lymphatic vessels (lymphangiogenesis) in cancer. These processes facilitate growth of solid tumours and metastatic spread of tumour cells to distant sites in the body. My research has focussed on molecular signaling by members of the vascular endothelial growth factor (VEGF) family of secreted glycoproteins. VEGF-A is a hemangiogenic protein expressed by many human tumours, and VEGF-C and VEGF-D can promote both hemangiogenesis and lymphangiogenesis in animal models of cancer. Expression of VEGF-C and VEGF-D in a range of human cancers has been reported to correlate with disease progression and lymph node metastasis. These growth factors signal via VEGFR-2 and VEGFR-3, cell surface receptor tyrosine kinases expressed on endothelial cells lining blood vessels and lymphatics in cancer. These signaling systems have been reported to be operative in prostate cancer, and could be targets for novel anti-cancer therapeutics designed to restrict tumour growth and spread in this disease. My laboratory has developed antibody and peptide inhibitors of signaling by VEGF-C and VEGF-D to restrict hemangiogenesis/lymphangiogenesis in prostate cancer – these reagents are currently in preclinical development. We are also exploring proteases that activate VEGF-C, VEGF-D and other growth factors with a view to targeting these molecules in prostate cancer.
Publications
1. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S-i, Kubo H and Achen MG. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nature Med. 7 (2001) 186-191.
2. Baldwin ME, Catimel B, Nice EC, Roufail S, Hall NE, Karkkainen MJ, Alitalo K, Stacker SA and Achen MG. The specificity of receptor binding by VEGF-D is different in mouse and man. J. Biol. Chem. 276 (2001) 19166-19171.
3. Achen MG, Williams RA, Baldwin ME, Lai P, Roufail S, Alitalo K and Stacker SA. The angiogenic and lymphangiogenic factor VEGF-D exhibits a paracrine mode of action in cancer. Growth Factors, 20 (2002) 99-107.
4. Stacker SA, Achen MG, Jussila L, Baldwin ME and Alitalo K. Lymphangiogenesis and cancer metastasis. Nature Rev. Cancer 2 (2002) 573-583.
5. McColl BK, Baldwin ME, Roufail S, Freeman C, Moritz RL, Simpson RJ, Alitalo K, Stacker SA and Achen MG. Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D. J. Exp. Med., 198 (2003) 863-868.
6. Zeng Y, Opeskin K, Baldwin ME, Horvath LG, Achen MG, Stacker SA, Sutherland RL and Williams ED. Expression of vascular endothelial growth factor (VEGF) receptor-3 by lymphatic endothelial cells is associated with lymph node metastasis in prostate cancer. Clin. Cancer Res., 10 (2004) 5137-5144.
7. Baldwin ME, Halford MM, Roufail S, Williams RA, Hibbs ML, Grail D, Kubo H, Stacker SA and Achen MG. VEGF-D is dispensible for development of the lymphatic system. Mol. Cell. Biol., 25 (2005) 2441-2449.
8. Achen MG, McColl BK and Stacker SA. Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 7 (2005) 121-127.
9. McColl BK, Paavonen K, Karnezis T, Harris NC, Davydova N, Rothaker J, Nice EC, Harder KW, Roufail S, Hibbs ML, Rogers PAW, Alitalo K, Stacker SA and Achen MG. Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2. FASEB J. 21 (2007) 1088-1098.