A tumor establishes a blood supply by secreting compounds that attract the growth of blood vessels (angiogenesis) from surrounding tissue.  This allows the tumor to grow more rapidly and to spread to distant sites in the body via blood vessels.  This latter process is known as metastatic spread and is the most lethal aspect of cancer. 

We and others have recently shown that tumors also attract the growth of lymphatic vessels (lymphangiogenesis) which facilitates metastatic spread via the lymphatics.  We seek to identify and characterize the vascular endothelial growth factors (VEGFs) secreted by tumor cells and the VEGF receptors on blood vessels and lymphatics that drive tumor angiogenesis and lymphangiogenesis. 

The long-term goal is to inhibit the action of these molecules in cancer to restrict tumor growth and metastatic spread.

Another focus of the laboratory is an alternative molecular signaling pathway involving the Wnt ligands and the Ryk receptor that is thought to be important in cancer biology. 

This intriguing pathway is essential for embryonic development and may play a role in the proliferation of cancer cells and tumor metastasis. 

A deeper understanding of this pathway will facilitate attempts to inhibit Wnt/Ryk signaling in the setting of cancer.  Our studies of signaling for tumor growth and metastasis involve technologies relating to molecular biology, cell biology, protein chemistry, developmental biology and genetic models of disease.         

Halford, M.M., Armes, J., Adams, M.T., Buchert, M., Meskenaite, V., Grail, D., Hibbs, M.L., Wilks A.F., Farlie, P.G., Newgreen, D.F., Hovens, C.M. and Stacker, S.A.  RYK-deficient mice exhibit craniofacial defects including a cleft palate associated with loss of crosstalk between RYK and Eph receptors.  Nat. Genet.  25:414-418, 2000.

Stacker, S.A., Caesar, C., Baldwin, M.E., Thornton, G.E., Williams R., Prevo, R., Jackson, D., Nishikawa, S-I., Kubo, H. and Achen M.G.  Vascular endothelial growth factor-D promotes the metastatic spread of cancer via the lymphatics. Nat. Med.  7:186-191, 2001.

Stacker, S.A., Achen, M.G., Jussila, L., Baldwin, M.E. and Alitalo, K.  Lymphangiogenesis and cancer metastasis.  Nat. Rev. Cancer 2:573-583, 2002.

McColl, B.K, Baldwin, M.E., Roufail, S., Freeman, C., Moritz., R.L., Simpson, R.J., Alitalo, K., Stacker, S.A. and Achen, M.G.  Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D.  J. Exp. Med.  198(6):863-8, 2003.

Achen, M.G., McColl, B.K., Stacker, S.A.  Focus on lymphangiogenesis in tumor metastasis.  Cancer Cell 7(2):121-7, 2005

Baldwin, M.E., Halford, M.M., Roufail, S., Williams, R.A., Hibbs, M.L, Grail, D., Kubo, H., Stacker, S.A., Achen, M.G.  Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol. Cell Biol. 25(6):2441-9, 2005

McColl, B.K,, Paavonen, K., Karnezis, T., Harris, N.C., Davydova, N., Rothacker, J., Nice E.C., Harder, K.W., Roufail, S., Hibbs, M.L., Rogers, P.A., Alitalo, K., Stacker, S.A., and Achen, M.G. Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2. FASEB Journal. (2007)

Shayan, R., Achen, M.G., and Stacker, S.A. Lymphatic vessels in cancer metastasis: bridging the gaps. Carcinogenesis. 27(9): 1729-38 (2006)

Stacker, S.A., Hughes, R.A., Williams, R.A., and Achen, M.G. Current strategies for modulating lymphangiogenesis signalling pathways in human disease. Current Medical Chemistry. 13(7): 783-92 (2006)

Click here for the ImageJ plug in used for Lymphatic Vessel Analysis (Shayan, R et al).